Allosteric Regulation of the Hsp90 Dynamics and Stability by Client Recruiter Cochaperones: Protein Structure Network Modeling
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Allosteric regulation of the Hsp90 dynamics and stability by client recruiter cochaperones: Protein structure network modeling", "type"=>"journal", "authors"=>[{"first_name"=>"Kristin", "last_name"=>"Blacklock", "scopus_author_id"=>"55756676300"}, {"first_name"=>"Gennady M.", "last_name"=>"Verkhivker", "scopus_author_id"=>"7003472684"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84903215285", "sgr"=>"84903215285", "pui"=>"372852844", "isbn"=>"1932-6203", "pmid"=>"24466147", "doi"=>"10.1371/journal.pone.0086547"}, "id"=>"49555ea2-4808-3c1d-bba7-d520140b6a33", "abstract"=>"The fundamental role of the Hsp90 chaperone in supporting functional activity of diverse protein clients is anchored by specific cochaperones. A family of immune sensing client proteins is delivered to the Hsp90 system with the aid of cochaperones Sgt1 and Rar1 that act cooperatively with Hsp90 to form allosterically regulated dynamic complexes. In this work, functional dynamics and protein structure network modeling are combined to dissect molecular mechanisms of Hsp90 regulation by the client recruiter cochaperones. Dynamic signatures of the Hsp90-cochaperone complexes are manifested in differential modulation of the conformational mobility in the Hsp90 lid motif. Consistent with the experiments, we have determined that targeted reorganization of the lid dynamics is a unifying characteristic of the client recruiter cochaperones. Protein network analysis of the essential conformational space of the Hsp90-cochaperone motions has identified structurally stable interaction communities, interfacial hubs and key mediating residues of allosteric communication pathways that act concertedly with the shifts in conformational equilibrium. The results have shown that client recruiter cochaperones can orchestrate global changes in the dynamics and stability of the interaction networks that could enhance the ATPase activity and assist in the client recruitment. The network analysis has recapitulated a broad range of structural and mutagenesis experiments, particularly clarifying the elusive role of Rar1 as a regulator of the Hsp90 interactions and a stability enhancer of the Hsp90-cochaperone complexes. Small-world organization of the interaction networks in the Hsp90 regulatory complexes gives rise to a strong correspondence between highly connected local interfacial hubs, global mediator residues of allosteric interactions and key functional hot spots of the Hsp90 activity. We have found that cochaperone-induced conformational changes in Hsp90 may be determined by specific interaction networks that can inhibit or promote progression of the ATPase cycle and thus control the recruitment of client proteins.", "link"=>"http://www.mendeley.com/research/allosteric-regulation-hsp90-dynamics-stability-client-recruiter-cochaperones-protein-structure-netwo", "reader_count"=>37, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>14, "Student > Master"=>7, "Student > Bachelor"=>3, "Lecturer"=>1, "Professor"=>5}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>5, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>14, "Student > Master"=>7, "Student > Bachelor"=>3, "Lecturer"=>1, "Professor"=>5}, "reader_count_by_subject_area"=>{"Unspecified"=>1, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>5, "Mathematics"=>1, "Agricultural and Biological Sciences"=>16, "Medicine and Dentistry"=>3, "Physics and Astronomy"=>1, "Chemistry"=>7, "Computer Science"=>1, "Earth and Planetary Sciences"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Chemistry"=>{"Chemistry"=>7}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>16}, "Computer Science"=>{"Computer Science"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>1}}, "reader_count_by_country"=>{"Turkey"=>1}, "group_count"=>0}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84903215285"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84903215285?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84903215285&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84903215285&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84903215285", "dc:identifier"=>"SCOPUS_ID:84903215285", "eid"=>"2-s2.0-84903215285", "dc:title"=>"Allosteric regulation of the Hsp90 dynamics and stability by client recruiter cochaperones: Protein structure network modeling", "dc:creator"=>"Blacklock K.", "prism:publicationName"=>"PLoS ONE", "prism:eIssn"=>"19326203", "prism:volume"=>"9", "prism:issueIdentifier"=>"1", "prism:pageRange"=>nil, "prism:coverDate"=>"2014-01-20", "prism:coverDisplayDate"=>"20 January 2014", "prism:doi"=>"10.1371/journal.pone.0086547", "citedby-count"=>"15", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"Rutgers, The State University of New Jersey", "affiliation-city"=>"New Brunswick", "affiliation-country"=>"United States"}, {"@_fa"=>"true", "affilname"=>"Chapman University", "affiliation-city"=>"Orange", "affiliation-country"=>"United States"}], "pubmed-id"=>"24466147", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e86547", "source-id"=>"10600153309", "openaccess"=>"1", "openaccessFlag"=>true}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fplosone%2Farticle%3Fid%3D10.1371%252Fjournal.pone.0086547", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"1", "year"=>"2014", "pdf_views"=>"57", "xml_views"=>"20", "html_views"=>"205"}
  • {"month"=>"2", "year"=>"2014", "pdf_views"=>"34", "xml_views"=>"0", "html_views"=>"91"}
  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"27", "xml_views"=>"1", "html_views"=>"83"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"29", "xml_views"=>"5", "html_views"=>"110"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"20", "xml_views"=>"0", "html_views"=>"72"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"16", "xml_views"=>"1", "html_views"=>"56"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"59"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"9", "xml_views"=>"2", "html_views"=>"21"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"13", "xml_views"=>"1", "html_views"=>"41"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"14", "xml_views"=>"2", "html_views"=>"50"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"14", "xml_views"=>"1", "html_views"=>"42"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"32"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"12", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"55"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"9", "xml_views"=>"1", "html_views"=>"25"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"36"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"29"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"28"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"34"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"19"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"44"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"24"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"12"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"13"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"32"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"21"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"12", "xml_views"=>"1", "html_views"=>"20"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"26"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"28"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"34"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"18"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"3", "html_views"=>"14"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"13"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"17"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"5", "xml_views"=>"2", "html_views"=>"26"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"1", "html_views"=>"58"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"9", "xml_views"=>"2", "html_views"=>"22"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"12"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"4"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"2", "html_views"=>"5"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"2"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"3", "html_views"=>"3"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"1", "html_views"=>"9"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"7"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"8"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"9"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"4"}
  • {"month"=>"2", "year"=>"2019", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"2"}
  • {"month"=>"3", "year"=>"2019", "pdf_views"=>"11", "xml_views"=>"0", "html_views"=>"6"}
  • {"month"=>"4", "year"=>"2019", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"5"}
  • {"month"=>"5", "year"=>"2019", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"3"}
  • {"month"=>"6", "year"=>"2019", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"2"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1351991"], "description"=>"<p>The dMD-derived fluctuation distance force constant profiles of the Hsp90-Sgt1 (A) and Hsp90-Sgt1-Rar1 complexes (B) were computed as implemented in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086547#pone.0086547-SacquinMora1\" target=\"_blank\">[96]</a>. The peaks in the distributions can correspond to the hinge sites. In the Hsp90-Sgt1 complex, the residue-based force constant profile of the Hsp90-NTD residues is shown in blue lines and the profile for the Sgt1-CS residues is in red lines. The force constant graph of the Hsp90-Sgt1-Rar1 complex is consistent with the coloring adopted in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086547#pone-0086547-g002\" target=\"_blank\">Figure 2</a>. The consecutive residue numbering is adopted in both complexes and is consistent with the annotation in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086547#pone-0086547-g002\" target=\"_blank\">Figure 2</a>. The position of the lid motif and the peaks corresponding to functionally important residues are indicated by arrows and annotated. The crystal structures of the Hsp90-Sgt1 (C) and Hsp90-Sgt1-Rar1 complexes (D) are annotated according to the domain coloring adopted in (A) and (B). The lid motif in both structures is highlighted and colored in gold; the anchoring residues with the high force constants are indicated. To streamline the comparison with structural and functional experiments, we annotated functional residues according to their original numbering in the crystal structures.</p>", "links"=>[], "tags"=>["biophysics", "Computational biology", "systems biology", "chemical biology", "computational chemistry", "Physical chemistry", "Computer applications", "Computer modeling", "Computerized simulations", "oncology", "Classical mechanics", "Statistical mechanics", "profiles", "hsp90-sgt1", "hsp90-sgt1-rar1"], "article_id"=>904640, "categories"=>["Information And Computing Sciences", "Biological Sciences", "Medicine", "Chemistry", "Physics"], "users"=>["Kristin Blacklock", "Gennady M. Verkhivker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0086547.g004", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Force_Constant_Profiles_of_the_Hsp90_Sgt1_and_Hsp90_Sgt1_Rar1_Complexes_/904640", "title"=>"The Force Constant Profiles of the Hsp90-Sgt1 and Hsp90-Sgt1-Rar1 Complexes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-20 03:45:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1352009"], "description"=>"<p>The residue-based centrality parameters: closeness (A) and betweenness (B) of the Hsp90-Cd37 complex. The centrality profile for the Hsp90-NTD residues is shown in red lines, and for the Cdc37-MD residues in blue lines. The consecutive residue numbering of the Hsp90-NTD and Cdc37-MD residues is adopted as in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086547#pone-0086547-g005\" target=\"_blank\">Figure 5</a>. The original numbering of the Hsp90-NTD (residues 14–223) in the NMR structure corresponds to residues 1–210, and the original numbering of the Cdc37-MD (residues 148–276) corresponds respectively to residues 211–339. The peaks in the centrality profiles corresponding to the functional hot spot residues of the Hsp90 activity are annotated and pointed by arrows. The lid residues in the Hsp90-Sgt1 and Hsp90-Sgt1-Rar1 complexes are highlighted and pointed to by oval circles surrounding the lid. To facilitate the comparison with structural and functional experiments, we annotated functional residues according to their original numbering in the crystal structures.</p>", "links"=>[], "tags"=>["biophysics", "Computational biology", "systems biology", "chemical biology", "computational chemistry", "Physical chemistry", "Computer applications", "Computer modeling", "Computerized simulations", "oncology", "Classical mechanics", "Statistical mechanics", "centrality", "networks", "hsp90-cdc37"], "article_id"=>904649, "categories"=>["Information And Computing Sciences", "Biological Sciences", "Medicine", "Chemistry", "Physics"], "users"=>["Kristin Blacklock", "Gennady M. Verkhivker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0086547.g010", "stats"=>{"downloads"=>1, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Centrality_Analysis_of_the_Interaction_Networks_in_the_Hsp90_Cdc37_Complex_/904649", "title"=>"The Centrality Analysis of the Interaction Networks in the Hsp90-Cdc37 Complex.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-20 03:45:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1352008"], "description"=>"<p>The residue-based centrality parameters: closeness (A, C) and betweenness (B, D) of the Hsp90-Sgt1 and Hsp90-Sgt1-Rar1 complexes. In (A) and (B) the centrality profile for the Hsp90-NTD residues is shown in red lines, and for the Sgt1-CS residues in blue lines. In (C) and (D) the centrality profile for the Hsp90-Sgt1-Rar1 residues is also colored according to their domain annotation. The Hsp90-NTD molecules are in red/blue; the Sgt1-CS molecules in green/brown; and the Rar1-CHORD2 molecules in orange/magenta. The peaks in the centrality profiles corresponding to the functional hot spot residues of the Hsp90 activity are annotated and pointed by arrows. The lid residues in the Hsp90-Sgt1 and Hsp90-Sgt1-Rar1 complexes are highlighted and pointed to by oval circles surrounding the lid. To streamline the comparison with structural and functional experiments, we annotated functional residues according to their original numbering in the crystal structures.</p>", "links"=>[], "tags"=>["biophysics", "Computational biology", "systems biology", "chemical biology", "computational chemistry", "Physical chemistry", "Computer applications", "Computer modeling", "Computerized simulations", "oncology", "Classical mechanics", "Statistical mechanics", "centrality", "networks", "hsp90-sgt1", "hsp90-sgt1-rar1"], "article_id"=>904648, "categories"=>["Information And Computing Sciences", "Biological Sciences", "Medicine", "Chemistry", "Physics"], "users"=>["Kristin Blacklock", "Gennady M. Verkhivker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0086547.g009", "stats"=>{"downloads"=>0, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Centrality_Analysis_of_the_Interaction_Networks_in_the_Hsp90_Sgt1_and_Hsp90_Sgt1_Rar1_Complexes_/904648", "title"=>"The Centrality Analysis of the Interaction Networks in the Hsp90-Sgt1 and Hsp90-Sgt1-Rar1 Complexes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-20 03:45:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1352006"], "description"=>"<p>(A) The degree of the interfacial hubs in the Hsp90-Cdc37 complex. The highly connected interfacial hubs with the number of connected residues exceeding the default threshold of four are shown for both complexes in filled blue bars. (B) Structural mapping of the interfacial hubs shown in (A) on the NMR structure of the Hsp90-Cdc37 complex (PDB ID 2K5B). The Hsp90-NTD is in blue ribbons, the Cdc37-MD is cyan ribbons. (C) The protein structure graphs of the major interfacial communities formed by in the Hsp90-Cdc37 complex. The graph illustrates the key role of the Cdc37-L205 residue hub in integrating a number of stable communities in the Hsp90-Cdc37 complex. The protein structure graphs were obtained using the CFinder program.</p>", "links"=>[], "tags"=>["biophysics", "Computational biology", "systems biology", "chemical biology", "computational chemistry", "Physical chemistry", "Computer applications", "Computer modeling", "Computerized simulations", "oncology", "Classical mechanics", "Statistical mechanics", "interfacial", "hubs", "hsp90-cdc37"], "article_id"=>904646, "categories"=>["Information And Computing Sciences", "Biological Sciences", "Medicine", "Chemistry", "Physics"], "users"=>["Kristin Blacklock", "Gennady M. Verkhivker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0086547.g008", "stats"=>{"downloads"=>0, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Distribution_of_the_Interfacial_Hubs_in_the_Hsp90_Cdc37_Complex_/904646", "title"=>"The Distribution of the Interfacial Hubs in the Hsp90-Cdc37 Complex.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-20 03:45:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1351994"], "description"=>"<p>The NMSF profile of the Hsp90-Cdc37 complex (A) was obtained using the NMR structure (PDB ID 2K5B) of the complex between human Cdc37 (Cdc37-MD, original residue numbering 148–276) and human Hsp90-NTD (original residue numbering 14–223) <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086547#pone.0086547-Sreeramulu1\" target=\"_blank\">[25]</a>. The residue-based NMSF values were computed by averaging the fluctuations over 20 low frequency modes. The NMSF profile for the Hsp90-NTD residues is shown in blue lines and for the Cdc37-MD residues in red lines. The consecutive residue numbering of the Hsp90-NTD and Cdc37-MD residues is adopted. The original numbering of the Hsp90-NTD (residues 14–223) in the NMR structure corresponds to residues 1–210, and the original numbering of the Cdc37-MD (residues 148–276) corresponds respectively to residues 211–339. (B) The fluctuation distance force constant profile of the Hsp90-Cdc37 complex. The profile is shown in blue lines for the Hsp90-NTD and in red lines for the Cdc37-MD. The consecutive residue numbering is adopted and is consistent with the annotation in (A). The position of the lid motif and the peaks corresponding to functionally important residues are indicated by arrows and annotated. The position of the lid motif (residues 108–138) is highlighted and pointed to by oval circles surrounding the lid. (C) Structural mapping of the conformational mobility in the essential conformational space of the three lowest frequency modes. A surface-based protein representation is employed. The color gradient from blue to red indicates the decreasing structural rigidity of protein residues. The interfacial residues are shown colored spheres according to their mobility. The important functional residues are annotated according to their original crystallographic numbering. (D) The Hsp90-Cdc37 structure is annotated according to the adopted domain coloring. The lid motif in both structures is highlighted and colored in gold; the anchoring residues with the high force constants are indicated.</p>", "links"=>[], "tags"=>["biophysics", "Computational biology", "systems biology", "chemical biology", "computational chemistry", "Physical chemistry", "Computer applications", "Computer modeling", "Computerized simulations", "oncology", "Classical mechanics", "Statistical mechanics", "mobility", "profiling", "hsp90-cdc37"], "article_id"=>904642, "categories"=>["Information And Computing Sciences", "Biological Sciences", "Medicine", "Chemistry", "Physics"], "users"=>["Kristin Blacklock", "Gennady M. Verkhivker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0086547.g005", "stats"=>{"downloads"=>0, "page_views"=>22, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Conformational_Mobility_Profiling_of_the_Hsp90_Cdc37_Complex_/904642", "title"=>"Conformational Mobility Profiling of the Hsp90-Cdc37 Complex.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-20 03:45:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1351988"], "description"=>"<p>The cross-correlation matrices of residue fluctuations in the Hsp90-Sgt1 (A) and in the Hsp90-Sgt1-Rar1 complex (B). The matrix was calculated using the ENM-derived normal modes of the refined structures. The axes denote Cα atoms of the protein residues in sequential order, so that each cell in the plot shows the isotropic correlation of two residues in the protein. Cross-correlations of residue-based fluctuations vary between +1 (fully correlated motion; fluctuation vectors in the same direction, colored in red) and −1 (fully anti-correlated motions; fluctuation vectors in the same direction, colored in blue). The consecutive residue indexing of the Hsp90-cochaperone complexes is adopted and is consistent with the detailed annotation in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086547#pone-0086547-g002\" target=\"_blank\">Figure 2</a>. The residue ranges for the domains in the Hsp90-Sgt1 and Hsp90-Sgt1-Rar1 complexes are mapped onto correlation maps. The position of the lid motif is indicated by a rectangular and the correlation of the lid with the rest of the protein is highlighted. (C) The Hsp90-Sgt1 structure is shown in a ribbon representation I (Hsp90-NTD in green, and Sgt1-CS in red). (D). The Hsp90-Sgt1-Rar1 structure is in ribbons with the Hsp90-NTD domain in red (molecule A) and blue (molecule B). The Sgt1-CS domains are shown in cyan (molecule C) and green (molecule D). The Rar1-CHORD2 domains are depicted in magenta (molecule E) and orange (molecule F).</p>", "links"=>[], "tags"=>["biophysics", "Computational biology", "systems biology", "chemical biology", "computational chemistry", "Physical chemistry", "Computer applications", "Computer modeling", "Computerized simulations", "oncology", "Classical mechanics", "Statistical mechanics", "correlated", "motions", "hsp90-sgt1", "hsp90-sgt1-rar1"], "article_id"=>904637, "categories"=>["Information And Computing Sciences", "Biological Sciences", "Medicine", "Chemistry", "Physics"], "users"=>["Kristin Blacklock", "Gennady M. Verkhivker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0086547.g003", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Analysis_of_the_Correlated_Motions_in_the_Hsp90_Sgt1_and_Hsp90_Sgt1_Rar1_Complexes_/904637", "title"=>"Analysis of the Correlated Motions in the Hsp90-Sgt1 and Hsp90-Sgt1-Rar1 Complexes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-20 03:45:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1351985"], "description"=>"<p>The residue-based NMSF profiles of the Hsp90-Sgt1 (A) and Hsp90-Sgt1-Rar1 complexes (B) were computed by averaging the fluctuations over 20 low frequency modes. In the Hsp90-Sgt1 complex, the NMSF profile of the Hsp90-NTD residues is shown in blue lines and the NMSF values for the Sgt1-CS residues are depicted in red lines. The consecutive residue numbering of the Hsp90-NTD and Sgt1-CS residues is adopted. The original numbering of the Hsp90-NTD residues (residues 4–217) from the crystal structure (PDB ID 2JKI) corresponds to residues 1–213 in panel (A). The crystal structure annotation of the Sgt1-CS domain (residues 151–240) corresponds to residues 215–304 in panel (A). The crystal structure of the HSP90-Sgt1-Rar1 complex (PDB ID 2XCM) is a heterohexamer with two molecules of each domain (B). The NMSF profiles for the Hsp90-NTD domains are shown in blue (molecule 1) and red (molecule 2); the NMSF graphs for the Sgt1-CS domain are in green (molecule 3) and cyan (molecule 4); the NMSF plots for the Rar1-CHORD2 domain are in orange (molecule 5) and magenta (molecule 6). The crystal structure residue numbering was converted to a consecutive numbering. The Hsp90-NTD residues are 1–213 (molecule 1) and 214–426 (molecule 2). The crystal structure numbering for the Sgt1-CS domain (residues 150–241) translates in consecutive residues 427–518 (molecule 3) and 519–610 (molecule 4). The crystal structure numbering for the Rar1-CHORD2 domain (residues 148–221) converted to residues 611–684 and 685–758. Structural distribution of conformational mobility in the essential conformational space of the Hsp90-Sgt1 (C) and Hsp90-Sgt1-Rar1 complexes (D) was obtained by averaging the residue fluctuations along the three lowest frequency modes. A surface-based protein representation is employed. The color gradient from blue to red indicates the decreasing structural rigidity (or increasing conformational mobility) of protein residues. The interfacial residues are shown spheres and colored according to their mobility. The ADP in the Hsp90-Sgt1 complex (C) is shown in atom-based colored spheres. The position and conformational mobility of the lid motif in the Hsp90-Sgt1 and Hsp90-Sgt1-Rar1 complexes are highlighted and pointed to by oval circles surrounding the lid.</p>", "links"=>[], "tags"=>["biophysics", "Computational biology", "systems biology", "chemical biology", "computational chemistry", "Physical chemistry", "Computer applications", "Computer modeling", "Computerized simulations", "oncology", "Classical mechanics", "Statistical mechanics", "residue-based", "fluctuation", "profiles", "hsp90-sgt1", "hsp90-sgt1-rar1"], "article_id"=>904633, "categories"=>["Information And Computing Sciences", "Biological Sciences", "Medicine", "Chemistry", "Physics"], "users"=>["Kristin Blacklock", "Gennady M. Verkhivker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0086547.g002", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Residue_Based_Fluctuation_Profiles_of_the_Hsp90_Sgt1_and_Hsp90_Sgt1_Rar1_Complexes_/904633", "title"=>"The Residue-Based Fluctuation Profiles of the Hsp90-Sgt1 and Hsp90-Sgt1-Rar1 Complexes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-20 03:45:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1352010", "https://ndownloader.figshare.com/files/1352011"], "description"=>"<div><p>The fundamental role of the Hsp90 chaperone in supporting functional activity of diverse protein clients is anchored by specific cochaperones. A family of immune sensing client proteins is delivered to the Hsp90 system with the aid of cochaperones Sgt1 and Rar1 that act cooperatively with Hsp90 to form allosterically regulated dynamic complexes. In this work, functional dynamics and protein structure network modeling are combined to dissect molecular mechanisms of Hsp90 regulation by the client recruiter cochaperones. Dynamic signatures of the Hsp90-cochaperone complexes are manifested in differential modulation of the conformational mobility in the Hsp90 lid motif. Consistent with the experiments, we have determined that targeted reorganization of the lid dynamics is a unifying characteristic of the client recruiter cochaperones. Protein network analysis of the essential conformational space of the Hsp90-cochaperone motions has identified structurally stable interaction communities, interfacial hubs and key mediating residues of allosteric communication pathways that act concertedly with the shifts in conformational equilibrium. The results have shown that client recruiter cochaperones can orchestrate global changes in the dynamics and stability of the interaction networks that could enhance the ATPase activity and assist in the client recruitment. The network analysis has recapitulated a broad range of structural and mutagenesis experiments, particularly clarifying the elusive role of Rar1 as a regulator of the Hsp90 interactions and a stability enhancer of the Hsp90-cochaperone complexes. Small-world organization of the interaction networks in the Hsp90 regulatory complexes gives rise to a strong correspondence between highly connected local interfacial hubs, global mediator residues of allosteric interactions and key functional hot spots of the Hsp90 activity. We have found that cochaperone-induced conformational changes in Hsp90 may be determined by specific interaction networks that can inhibit or promote progression of the ATPase cycle and thus control the recruitment of client proteins.</p></div>", "links"=>[], "tags"=>["biophysics", "Computational biology", "systems biology", "chemical biology", "computational chemistry", "Physical chemistry", "Computer applications", "Computer modeling", "Computerized simulations", "oncology", "Classical mechanics", "Statistical mechanics", "hsp90", "recruiter"], "article_id"=>904650, "categories"=>["Information And Computing Sciences", "Biological Sciences", "Medicine", "Chemistry", "Physics"], "users"=>["Kristin Blacklock", "Gennady M. Verkhivker"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0086547.s001", "https://dx.doi.org/10.1371/journal.pone.0086547.s002"], "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Allosteric_Regulation_of_the_Hsp90_Dynamics_and_Stability_by_Client_Recruiter_Cochaperones_Protein_Structure_Network_Modeling_/904650", "title"=>"Allosteric Regulation of the Hsp90 Dynamics and Stability by Client Recruiter Cochaperones: Protein Structure Network Modeling", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-01-20 03:45:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1351978"], "description"=>"<p>In this model, ATP binding to the Hsp90-NTD of apo-Hsp90 in the open form can induce a fast dynamic exchange between a nucleotide-free Hsp90 and an ATP-bound state in which the ATP lids and Hsp90-NTDs are still open. Binding of Rar1-CHORD1 to the Hsp90-NTD intersects the normal progression of the ATPase cycle by preventing the lid enclosure of ATP and inhibiting the formation of the closed Hsp90 dimer. This interaction supports the binding of Rar1-CHORD2 to the other Hsp90-NTD in the other protomer. Upon binding of both Rar1-CHORD domains, SGT1 is recruited to interact with the Hsp90-NTD and Rar1-CHORD2 domain. Cochaperone-mediated arrest of the Hsp90-ATPase conformational cycle in the open form promotes the assembly of the ternary Hsp90-Sgt1-Rar1 complex and recruitment of the NLR clients. In the ternary complex, the fluctuations of the lid segment may allow the catalytic Arg residue from the Hsp90-MD to reach the nucleotide binding site and induce ATP hydrolysis. The Rar1-stimulated hydrolysis of ATP would lead to dissociation of RAR1, SGT1, and NLR client from the Hsp90 dimer. After ATP is hydrolyzed, the Hsp90-NTDs domains dissociate and ADP is released returning Hsp90 to the nucleotide-free open state. The Hsp90 structure is shown in a surface representation with an annotation of structural elements. The Hsp90-NTD is shown in green; the Hsp90-MD is depicted in blue and the Hsp90-CTD is presented in red.</p>", "links"=>[], "tags"=>["biophysics", "Computational biology", "systems biology", "chemical biology", "computational chemistry", "Physical chemistry", "Computer applications", "Computer modeling", "Computerized simulations", "oncology", "Classical mechanics", "Statistical mechanics", "hsp90-atpase", "cochaperones", "sgt1"], "article_id"=>904631, "categories"=>["Information And Computing Sciences", "Biological Sciences", "Medicine", "Chemistry", "Physics"], "users"=>["Kristin Blacklock", "Gennady M. Verkhivker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0086547.g001", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_Model_of_the_Hsp90_ATPase_Cycle_The_Functional_Role_of_the_Cochaperones_Sgt1_and_Rar1_/904631", "title"=>"A Model of the Hsp90-ATPase Cycle: The Functional Role of the Cochaperones Sgt1 and Rar1.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-20 03:45:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1352005"], "description"=>"<p>The degree of the interfacial hubs in the Hsp90-Sgt1 complex (A) and Hsp90-Sgt1-Rar1 complex (B). The degree of a hub (or degree centrality) is the simplest measure of centrality and is defined as the number of links incident upon a node. The highly connected interfacial hubs with the number of connected residues exceeding the default threshold of four are shown for both complexes in filled blue bars. (C) Structural mapping of the interfacial hubs shown in (A) on the crystal structure of the Hsp90-Sgt1 complex (PDB ID 2JKI). The Hsp90-NTD is in blue ribbons, the Sgt1-CS domain is cyan ribbons. (D) Structural mapping of the interfacial hubs shown in (B) on the crystal structure of the Hsp90-Sgt1-Rar1 complex (PDB ID 2XCM). In the heterohexamer Hsp90-Sgt1-Rar1 complex, the two Hsp90-NTD molecules are shown in blue and red ribbons; the two Sgt1-CS domains are presented in cyan and green ribbons; and the two Rar1-CHORD2 domains are depicted in orange and magenta ribbons respectively. The interfacial residue hubs in (C) and (D) are mapped as spheres and annotated according to their domain color.</p>", "links"=>[], "tags"=>["biophysics", "Computational biology", "systems biology", "chemical biology", "computational chemistry", "Physical chemistry", "Computer applications", "Computer modeling", "Computerized simulations", "oncology", "Classical mechanics", "Statistical mechanics", "interfacial", "hubs", "hsp90-sgt1", "hsp90-sgt1-rar1"], "article_id"=>904645, "categories"=>["Information And Computing Sciences", "Biological Sciences", "Medicine", "Chemistry", "Physics"], "users"=>["Kristin Blacklock", "Gennady M. Verkhivker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0086547.g007", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_Distribution_of_the_Interfacial_Hubs_in_the_Hsp90_Sgt1_and_Hsp90_Sgt1_Rar1_Complexes_/904645", "title"=>"The Distribution of the Interfacial Hubs in the Hsp90-Sgt1 and Hsp90-Sgt1-Rar1 Complexes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-20 03:45:40"}
  • {"files"=>["https://ndownloader.figshare.com/files/1352004"], "description"=>"<p>(A) The distributions of the interfacial cliques (in blue filled bars) and the interfacial communities (in red filled bars) in ternary complex are shown respectively for the Hsp90-Sgt1, Hsp90-Rar1 and Rar1-Sgt1 binding interfaces. (B) The distribution of all residue hubs (in blue filled bars) and the interfacial hubs (in red filled bars) in the Hsp90-NTD, Sgt1-CS and Rar1-CHORD2 domains. (C) A close-up of structurally stable communities formed by the Rar1-CHORD2 residues with the Hsp90-NTD (Rar1-F187, Rar1-F204, Rar1-F207, Hsp90-F49) and the Sgt1-CS domain (Rar1-E175, Rar1-W217, Sgt1-Q184, Sgt1-H239). The interacting domains are annotated and shown in ribbons, Rar1-CHORD2 is colored in magenta, Hsp90-NTD is in red, and the Sgt1-CS is in cyan. The residues contributing to the interfacial communities are indicated. (D) The protein structure graphs of the major interfacial communities formed by the Rar1-CHORD2 domain in the heterohexamer Hsp90-Sgt1-Rar1 complex. The annotation of the interacting domains is consistent with <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086547#pone-0086547-g003\" target=\"_blank\">Figure 3</a>. The Hsp90-NTD domain (molecules A and B) interacts respectively with the Rar1-CHORD2 domain (molecules E and F). The Rar1-CHORD2 molecules E and F interact with the Sgt1-CS molecules C and D respectively. The protein structure graphs were obtained using the CFinder program <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086547#pone.0086547-Palla1\" target=\"_blank\">[104]</a>.</p>", "links"=>[], "tags"=>["biophysics", "Computational biology", "systems biology", "chemical biology", "computational chemistry", "Physical chemistry", "Computer applications", "Computer modeling", "Computerized simulations", "oncology", "Classical mechanics", "Statistical mechanics", "hsp90-sgt1-rar1"], "article_id"=>904644, "categories"=>["Information And Computing Sciences", "Biological Sciences", "Medicine", "Chemistry", "Physics"], "users"=>["Kristin Blacklock", "Gennady M. Verkhivker"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0086547.g006", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Network_Analysis_of_the_Hsp90_Sgt1_Rar1_Complex_/904644", "title"=>"Network Analysis of the Hsp90-Sgt1-Rar1 Complex.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-20 03:45:40"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"1", "full-text"=>"0", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
  • {"unique-ip"=>"26", "full-text"=>"21", "pdf"=>"21", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
  • {"unique-ip"=>"10", "full-text"=>"4", "pdf"=>"3", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"10", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"unique-ip"=>"8", "full-text"=>"4", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"21", "full-text"=>"19", "pdf"=>"15", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"10", "full-text"=>"11", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"6", "full-text"=>"11", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"23", "full-text"=>"33", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"18", "full-text"=>"14", "pdf"=>"8", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"15", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"4", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"15", "full-text"=>"10", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"15", "full-text"=>"13", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"unique-ip"=>"9", "full-text"=>"9", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"12", "full-text"=>"10", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"8", "full-text"=>"6", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"unique-ip"=>"15", "full-text"=>"14", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2015", "month"=>"1"}
  • {"unique-ip"=>"12", "full-text"=>"9", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"13", "full-text"=>"9", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"4"}
  • {"unique-ip"=>"8", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"10", "full-text"=>"7", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"7", "full-text"=>"5", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"unique-ip"=>"8", "full-text"=>"4", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"8"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"9"}
  • {"unique-ip"=>"9", "full-text"=>"6", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"11"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"1", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"3", "full-text"=>"4", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"7", "full-text"=>"11", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"3", "full-text"=>"5", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2019", "month"=>"1"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"4"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"5"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"6"}
  • {"unique-ip"=>"11", "full-text"=>"11", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"1", "full-text"=>"1", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"11", "full-text"=>"7", "pdf"=>"5", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"5", "full-text"=>"7", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"11", "full-text"=>"3", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[291]}, {"subject_area"=>"/Biology and life sciences/Molecular biology", "average_usage"=>[292, 461]}, {"subject_area"=>"/Computer and information sciences", "average_usage"=>[327, 511]}, {"subject_area"=>"/Computer and information sciences/Network analysis", "average_usage"=>[347, 531]}, {"subject_area"=>"/Physical sciences/Physics", "average_usage"=>[266]}]}
Loading … Spinner
There are currently no alerts