Dynamic Control of Selectivity in the Ubiquitination Pathway Revealed by an ASP to GLU Substitution in an Intra-Molecular Salt-Bridge Network
Publication Date
November 01, 2012
Journal
PLOS Computational Biology
Authors
Sjoerd J. L. Van Wijk, Adrien S. J. Melquiond, Sjoerd J. De Vries, H. Th. Marc Timmers, et al
Volume
8
Issue
11
Pages
e1002754
DOI
http://doi.org/10.1371/journal.pcbi.1002754
Publisher URL
http://journals.plos.org/ploscompbiol/article?id=10.1371%2Fjournal.pcbi.1002754
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/23133359
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3486841
Europe PMC
http://europepmc.org/abstract/MED/23133359
Web of Science
000311897100013
Scopus
84870667444
Mendeley
http://www.mendeley.com/research/dynamic-control-selectivity-ubiquitination-pathway-revealed-asp-glu-substitution-intramolecular-salt
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Dynamic Control of Selectivity in the Ubiquitination Pathway Revealed by an ASP to GLU Substitution in an Intra-Molecular Salt-Bridge Network", "type"=>"journal", "authors"=>[{"first_name"=>"Sjoerd J L", "last_name"=>"van Wijk", "scopus_author_id"=>"8577923700"}, {"first_name"=>"Adrien S J", "last_name"=>"Melquiond", "scopus_author_id"=>"8341734500"}, {"first_name"=>"Sjoerd J.", "last_name"=>"de Vries", "scopus_author_id"=>"8608761200"}, {"first_name"=>"H. Th Marc", "last_name"=>"Timmers", "scopus_author_id"=>"55508547300"}, {"first_name"=>"Alexandre M J J", "last_name"=>"Bonvin", "scopus_author_id"=>"7003870500"}], "year"=>2012, "source"=>"PLoS Computational Biology", "identifiers"=>{"issn"=>"1553734X", "pui"=>"366216210", "scopus"=>"2-s2.0-84870667444", "pmid"=>"23133359", "doi"=>"10.1371/journal.pcbi.1002754", "isbn"=>"1553-7358 (Electronic)\\r1553-734X (Linking)", "sgr"=>"84870667444"}, "id"=>"6fcc37c8-6d1b-3a97-b42a-6dda1864bc3a", "abstract"=>"Ubiquitination relies on a subtle balance between selectivity and promiscuity achieved through specific interactions between ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s). Here, we report how a single aspartic to glutamic acid substitution acts as a dynamic switch to tip the selectivity balance of human E2s for interaction toward E3 RING-finger domains. By combining molecular dynamic simulations, experimental yeast-two-hybrid screen of E2-E3 (RING) interactions and mutagenesis, we reveal how the dynamics of an internal salt-bridge network at the rim of the E2-E3 interaction surface controls the balance between an \"open\", binding competent, and a \"closed\", binding incompetent state. The molecular dynamic simulations shed light on the fine mechanism of this molecular switch and allowed us to identify its components, namely an aspartate/glutamate pair, a lysine acting as the central switch and a remote aspartate. Perturbations of single residues in this network, both inside and outside the interaction surface, are sufficient to switch the global E2 interaction selectivity as demonstrated experimentally. Taken together, our results indicate a new mechanism to control E2-E3 interaction selectivity at an atomic level, highlighting how minimal changes in amino acid side-chain affecting the dynamics of intramolecular salt-bridges can be crucial for protein-protein interactions. These findings indicate that the widely accepted sequence-structure-function paradigm should be extended to sequence-structure-dynamics-function relationship and open new possibilities for control and fine-tuning of protein interaction selectivity.", "link"=>"http://www.mendeley.com/research/dynamic-control-selectivity-ubiquitination-pathway-revealed-asp-glu-substitution-intramolecular-salt", "reader_count"=>22, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>7, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>4, "Student > Ph. D. Student"=>7, "Student > Postgraduate"=>1, "Student > Master"=>7, "Student > Bachelor"=>1, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>5, "Agricultural and Biological Sciences"=>13, "Chemistry"=>3, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Chemistry"=>{"Chemistry"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>13}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}}, "reader_count_by_country"=>{"Netherlands"=>1, "United Kingdom"=>1, "France"=>1}, "group_count"=>1}

CrossRef

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84870667444"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/84870667444?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84870667444&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=84870667444&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/84870667444", "dc:identifier"=>"SCOPUS_ID:84870667444", "eid"=>"2-s2.0-84870667444", "dc:title"=>"Dynamic Control of Selectivity in the Ubiquitination Pathway Revealed by an ASP to GLU Substitution in an Intra-Molecular Salt-Bridge Network", "dc:creator"=>"van Wijk S.", "prism:publicationName"=>"PLoS Computational Biology", "prism:issn"=>"1553734X", "prism:eIssn"=>"15537358", "prism:volume"=>"8", "prism:issueIdentifier"=>"11", "prism:pageRange"=>nil, "prism:coverDate"=>"2012-11-01", "prism:coverDisplayDate"=>"November 2012", "prism:doi"=>"10.1371/journal.pcbi.1002754", "citedby-count"=>"6", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"University Medical Center Utrecht", "affiliation-city"=>"Utrecht", "affiliation-country"=>"Netherlands"}, {"@_fa"=>"true", "affilname"=>"Klinikum und Fachbereich Medizin Johann Wolfgang Goethe-Universitat Frankfurt am Main", "affiliation-city"=>"Frankfurt am Main", "affiliation-country"=>"Germany"}], "pubmed-id"=>"23133359", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e1002754", "source-id"=>"4000151810"}

Facebook

  • {"url"=>"http%3A%2F%2Fjournals.plos.org%2Fploscompbiol%2Farticle%3Fid%3D10.1371%252Fjournal.pcbi.1002754", "share_count"=>0, "like_count"=>0, "comment_count"=>0, "click_count"=>0, "total_count"=>0}

Counter

  • {"month"=>"11", "year"=>"2012", "pdf_views"=>"76", "xml_views"=>"7", "html_views"=>"563"}
  • {"month"=>"12", "year"=>"2012", "pdf_views"=>"24", "xml_views"=>"8", "html_views"=>"171"}
  • {"month"=>"1", "year"=>"2013", "pdf_views"=>"10", "xml_views"=>"0", "html_views"=>"79"}
  • {"month"=>"2", "year"=>"2013", "pdf_views"=>"8", "xml_views"=>"2", "html_views"=>"348"}
  • {"month"=>"3", "year"=>"2013", "pdf_views"=>"10", "xml_views"=>"1", "html_views"=>"68"}
  • {"month"=>"4", "year"=>"2013", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"51"}
  • {"month"=>"5", "year"=>"2013", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"62"}
  • {"month"=>"6", "year"=>"2013", "pdf_views"=>"10", "xml_views"=>"10", "html_views"=>"55"}
  • {"month"=>"7", "year"=>"2013", "pdf_views"=>"7", "xml_views"=>"12", "html_views"=>"35"}
  • {"month"=>"8", "year"=>"2013", "pdf_views"=>"4", "xml_views"=>"7", "html_views"=>"41"}
  • {"month"=>"9", "year"=>"2013", "pdf_views"=>"7", "xml_views"=>"5", "html_views"=>"43"}
  • {"month"=>"10", "year"=>"2013", "pdf_views"=>"2", "xml_views"=>"3", "html_views"=>"41"}
  • {"month"=>"11", "year"=>"2013", "pdf_views"=>"6", "xml_views"=>"1", "html_views"=>"42"}
  • {"month"=>"12", "year"=>"2013", "pdf_views"=>"5", "xml_views"=>"12", "html_views"=>"95"}
  • {"month"=>"1", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"27", "html_views"=>"48"}
  • {"month"=>"2", "year"=>"2014", "pdf_views"=>"1", "xml_views"=>"8", "html_views"=>"52"}
  • {"month"=>"3", "year"=>"2014", "pdf_views"=>"4", "xml_views"=>"11", "html_views"=>"36"}
  • {"month"=>"4", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"11", "html_views"=>"49"}
  • {"month"=>"5", "year"=>"2014", "pdf_views"=>"5", "xml_views"=>"11", "html_views"=>"38"}
  • {"month"=>"6", "year"=>"2014", "pdf_views"=>"3", "xml_views"=>"12", "html_views"=>"39"}
  • {"month"=>"7", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"6", "html_views"=>"39"}
  • {"month"=>"8", "year"=>"2014", "pdf_views"=>"3", "xml_views"=>"17", "html_views"=>"28"}
  • {"month"=>"9", "year"=>"2014", "pdf_views"=>"1", "xml_views"=>"12", "html_views"=>"18"}
  • {"month"=>"10", "year"=>"2014", "pdf_views"=>"7", "xml_views"=>"8", "html_views"=>"43"}
  • {"month"=>"11", "year"=>"2014", "pdf_views"=>"6", "xml_views"=>"16", "html_views"=>"44"}
  • {"month"=>"12", "year"=>"2014", "pdf_views"=>"1", "xml_views"=>"16", "html_views"=>"28"}
  • {"month"=>"1", "year"=>"2015", "pdf_views"=>"0", "xml_views"=>"7", "html_views"=>"14"}
  • {"month"=>"2", "year"=>"2015", "pdf_views"=>"13", "xml_views"=>"15", "html_views"=>"21"}
  • {"month"=>"3", "year"=>"2015", "pdf_views"=>"20", "xml_views"=>"11", "html_views"=>"25"}
  • {"month"=>"4", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"29", "html_views"=>"26"}
  • {"month"=>"5", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"20", "html_views"=>"20"}
  • {"month"=>"6", "year"=>"2015", "pdf_views"=>"1", "xml_views"=>"14", "html_views"=>"21"}
  • {"month"=>"7", "year"=>"2015", "pdf_views"=>"21", "xml_views"=>"24", "html_views"=>"29"}
  • {"month"=>"8", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"12", "html_views"=>"29"}
  • {"month"=>"9", "year"=>"2015", "pdf_views"=>"3", "xml_views"=>"20", "html_views"=>"17"}
  • {"month"=>"10", "year"=>"2015", "pdf_views"=>"7", "xml_views"=>"16", "html_views"=>"16"}
  • {"month"=>"11", "year"=>"2015", "pdf_views"=>"2", "xml_views"=>"20", "html_views"=>"24"}
  • {"month"=>"12", "year"=>"2015", "pdf_views"=>"5", "xml_views"=>"12", "html_views"=>"38"}
  • {"month"=>"1", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"20", "html_views"=>"35"}
  • {"month"=>"2", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"3", "html_views"=>"9"}
  • {"month"=>"3", "year"=>"2016", "pdf_views"=>"1", "xml_views"=>"15", "html_views"=>"22"}
  • {"month"=>"4", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"2", "html_views"=>"19"}
  • {"month"=>"5", "year"=>"2016", "pdf_views"=>"5", "xml_views"=>"0", "html_views"=>"15"}
  • {"month"=>"6", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"7", "year"=>"2016", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"8", "year"=>"2016", "pdf_views"=>"3", "xml_views"=>"0", "html_views"=>"17"}
  • {"month"=>"9", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"10", "year"=>"2016", "pdf_views"=>"7", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"11", "year"=>"2016", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"8"}
  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"10"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"27"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"2", "xml_views"=>"0", "html_views"=>"38"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"1", "xml_views"=>"1", "html_views"=>"20"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"0", "xml_views"=>"0", "html_views"=>"20"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"4", "xml_views"=>"1", "html_views"=>"31"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"22"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"3", "xml_views"=>"2", "html_views"=>"7"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"1", "xml_views"=>"1", "html_views"=>"31"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"27"}

Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/549630"], "description"=>"<p><b>A.</b> Atomic view of the UbcH6/UbcH8 intra-molecular salt-bridge network that controls E105/D113 positioning and E3 binding. Images were generated with the PyMOL Molecular Graphics System, Version 1.3 <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002754#pcbi.1002754-Schrdinger1\" target=\"_blank\">[38]</a>. <b>B.</b> Dynamics of the intra-molecular salt-bridge network. Depicted are E2-specific distances between the indicated side-chains during a 20 ns MD trajectory. Curves were smoothened using a 100 ps running average window.</p>", "links"=>[], "tags"=>["e2", "intra-molecular", "salt-bridge"], "article_id"=>220120, "categories"=>["Biochemistry", "Biological Sciences", "Chemistry", "Information And Computing Sciences", "Biophysics"], "users"=>["Sjoerd J. L. van Wijk", "Adrien S. J. Melquiond", "Sjoerd J. de Vries", "H. Th. Marc Timmers", "Alexandre M. J. J. Bonvin"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1002754.g003", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Properties_of_the_E2_intra_molecular_salt_bridge_network_/220120", "title"=>"Properties of the E2 intra-molecular salt-bridge network.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-01 00:02:00"}
  • {"files"=>["https://ndownloader.figshare.com/files/549773"], "description"=>"<p><b>A.</b> Perturbation of critical network components displaces E105/D113 and controls E3 binding. Mutagenesis of strictly conserved residues that mediate the bridging status of D113 in UbcH8 were mutated to challenge the MD predictions (see main text and Material and Methods section for details). <b>B.</b> Schematic representation of the “open” and “bridged” conformations of the intra-molecular network controlling E3 interactions. Indicated are E2-specific residues as well as the conserved network residues that mediate E3 binding.</p>", "links"=>[], "tags"=>["salt-bridge", "controls", "e3"], "article_id"=>220264, "categories"=>["Biochemistry", "Biological Sciences", "Chemistry", "Information And Computing Sciences", "Biophysics"], "users"=>["Sjoerd J. L. van Wijk", "Adrien S. J. Melquiond", "Sjoerd J. de Vries", "H. Th. Marc Timmers", "Alexandre M. J. J. Bonvin"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1002754.g004", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Validation_of_the_dynamic_salt_bridge_network_that_controls_RING_E3_interaction_selectivity_/220264", "title"=>"Validation of the dynamic salt-bridge network that controls RING E3 interaction selectivity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-01 00:04:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/549333"], "description"=>"<p><b>A.</b> Sequence alignment of human UbcH6 (UBE2E1) and UbcH8 (UBE2E2). Secondary structures and E3-interface regions (H1, L1 and L2) are indicated. Arrows indicate E2-specific residues; asterisks indicate conserved residues involved in bridging. N-terminal extensions are indicated as shaded. <b>B.</b> E3-interaction profiles of <i>wt</i> UbcH6, UbcH8 and UbcH8 D113E (see <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002754#s4\" target=\"_blank\">Materials and Methods</a> section for details).</p>", "links"=>[], "tags"=>["ubch6", "ubch8", "e2", "enzymes", "e3", "domains"], "article_id"=>219819, "categories"=>["Biochemistry", "Biological Sciences", "Chemistry", "Information And Computing Sciences", "Biophysics"], "users"=>["Sjoerd J. L. van Wijk", "Adrien S. J. Melquiond", "Sjoerd J. de Vries", "H. Th. Marc Timmers", "Alexandre M. J. J. Bonvin"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1002754.g001", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_highly_similar_UbcH6_and_UbcH8_E2_enzymes_interact_with_different_RING_E3_domains_cohorts_/219819", "title"=>"The highly similar UbcH6 and UbcH8 E2 enzymes interact with different RING E3 domains cohorts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-01 02:43:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/549515"], "description"=>"<p><b>A</b>. MD simulation cross profiles of UbcH6 and UbcH8 depicting cross-RMSDs calculated over all E2s Cαs and Cβs in the same trajectory. <b>B</b>. Electrostatic potentials mapped onto the solvent accessible surface of UbcH6 and UbcH8. Two views of each protein are shown (low electron density: blue; high electron density: red; neutral: white). The electrostatic potential surfaces were determined using the Adaptive Poisson-Boltzmann Solver package (APBS) <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002754#pcbi.1002754-Baker1\" target=\"_blank\">[37]</a> within PyMOL <a href=\"http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1002754#pcbi.1002754-Schrdinger1\" target=\"_blank\">[38]</a>.</p>", "links"=>[], "tags"=>["electrostatic", "potentials", "conformational", "ubch6", "ubch8"], "article_id"=>220004, "categories"=>["Biochemistry", "Biological Sciences", "Chemistry", "Information And Computing Sciences", "Biophysics"], "users"=>["Sjoerd J. L. van Wijk", "Adrien S. J. Melquiond", "Sjoerd J. de Vries", "H. Th. Marc Timmers", "Alexandre M. J. J. Bonvin"], "doi"=>"https://dx.doi.org/10.1371/journal.pcbi.1002754.g002", "stats"=>{"downloads"=>3, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Study_of_electrostatic_potentials_and_conformational_stability_of_UbcH6_and_UbcH8_enzymes_/220004", "title"=>"Study of electrostatic potentials and conformational stability of UbcH6 and UbcH8 enzymes.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-11-01 00:00:04"}
  • {"files"=>["https://ndownloader.figshare.com/files/293050", "https://ndownloader.figshare.com/files/293128"], "description"=>"<div><p>Ubiquitination relies on a subtle balance between selectivity and promiscuity achieved through specific interactions between ubiquitin-conjugating enzymes (E2s) and ubiquitin ligases (E3s). Here, we report how a single aspartic to glutamic acid substitution acts as a dynamic switch to tip the selectivity balance of human E2s for interaction toward E3 RING-finger domains. By combining molecular dynamic simulations, experimental yeast-two-hybrid screen of E2-E3 (RING) interactions and mutagenesis, we reveal how the dynamics of an internal salt-bridge network at the rim of the E2-E3 interaction surface controls the balance between an “open”, binding competent, and a “closed”, binding incompetent state. The molecular dynamic simulations shed light on the fine mechanism of this molecular switch and allowed us to identify its components, namely an aspartate/glutamate pair, a lysine acting as the central switch and a remote aspartate. Perturbations of single residues in this network, both inside and outside the interaction surface, are sufficient to switch the global E2 interaction selectivity as demonstrated experimentally. Taken together, our results indicate a new mechanism to control E2-E3 interaction selectivity at an atomic level, highlighting how minimal changes in amino acid side-chain affecting the dynamics of intramolecular salt-bridges can be crucial for protein-protein interactions. These findings indicate that the widely accepted sequence-structure-function paradigm should be extended to <em>sequence-structure-dynamics-function</em> relationship and open new possibilities for control and fine-tuning of protein interaction selectivity.</p> </div>", "links"=>[], "tags"=>["selectivity", "ubiquitination", "pathway", "revealed", "asp", "glu", "substitution", "intra-molecular", "salt-bridge", "network"], "article_id"=>117685, "categories"=>["Biochemistry", "Biological Sciences", "Chemistry", "Information And Computing Sciences", "Biophysics"], "users"=>["Sjoerd J. L. van Wijk", "Adrien S. J. Melquiond", "Sjoerd J. de Vries", "H. Th. Marc Timmers", "Alexandre M. J. J. Bonvin"], "doi"=>["https://dx.doi.org/10.1371/journal.pcbi.1002754.s001", "https://dx.doi.org/10.1371/journal.pcbi.1002754.s002"], "stats"=>{"downloads"=>2, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Dynamic_Control_of_Selectivity_in_the_Ubiquitination_Pathway_Revealed_by_an_ASP_to_GLU_Substitution_in_an_Intra_Molecular_Salt_Bridge_Network__/117685", "title"=>"Dynamic Control of Selectivity in the Ubiquitination Pathway Revealed by an ASP to GLU Substitution in an Intra-Molecular Salt-Bridge Network", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-11-01 02:08:05"}

PMC Usage Stats | Further Information

  • {"unique-ip"=>"9", "full-text"=>"20", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"12"}
  • {"unique-ip"=>"15", "full-text"=>"20", "pdf"=>"2", "abstract"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"9", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"1"}
  • {"unique-ip"=>"13", "full-text"=>"13", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"2"}
  • {"unique-ip"=>"9", "full-text"=>"11", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"3"}
  • {"unique-ip"=>"11", "full-text"=>"9", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"4"}
  • {"unique-ip"=>"24", "full-text"=>"15", "pdf"=>"5", "abstract"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2012", "month"=>"11"}
  • {"unique-ip"=>"7", "full-text"=>"13", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"5"}
  • {"unique-ip"=>"8", "full-text"=>"13", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"6"}
  • {"unique-ip"=>"5", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"4", "cited-by"=>"0", "year"=>"2013", "month"=>"7"}
  • {"unique-ip"=>"4", "full-text"=>"8", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2013", "month"=>"8"}
  • {"unique-ip"=>"9", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"9"}
  • {"unique-ip"=>"2", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"10"}
  • {"unique-ip"=>"2", "full-text"=>"4", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"11"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2013", "month"=>"12"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2014", "month"=>"1"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"2"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"3"}
  • {"unique-ip"=>"15", "full-text"=>"16", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"5"}
  • {"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"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"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"=>"2014", "month"=>"7"}
  • {"unique-ip"=>"13", "full-text"=>"10", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"8"}
  • {"unique-ip"=>"7", "full-text"=>"8", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"9"}
  • {"unique-ip"=>"23", "full-text"=>"30", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"10"}
  • {"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"=>"2014", "month"=>"11"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2014", "month"=>"12"}
  • {"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"=>"1"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"2"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"3"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"4"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"5"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"6"}
  • {"unique-ip"=>"5", "full-text"=>"6", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"7"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"8"}
  • {"unique-ip"=>"5", "full-text"=>"4", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"9"}
  • {"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"=>"2015", "month"=>"10"}
  • {"unique-ip"=>"4", "full-text"=>"2", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2015", "month"=>"11"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2015", "month"=>"12"}
  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"1"}
  • {"unique-ip"=>"2", "full-text"=>"2", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"2"}
  • {"unique-ip"=>"2", "full-text"=>"1", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"3"}
  • {"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"=>"4"}
  • {"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"=>"2016", "month"=>"5"}
  • {"unique-ip"=>"4", "full-text"=>"6", "pdf"=>"0", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"6"}
  • {"unique-ip"=>"2", "full-text"=>"1", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"7"}
  • {"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"=>"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"=>"2016", "month"=>"9"}
  • {"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"=>"2016", "month"=>"10"}
  • {"unique-ip"=>"5", "full-text"=>"5", "pdf"=>"2", "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"=>"2", "pdf"=>"2", "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"=>"4", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"1", "full-text"=>"0", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"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"=>"2017", "month"=>"5"}
  • {"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"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"2", "full-text"=>"1", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "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"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"3", "full-text"=>"1", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}

Relative Metric

{"start_date"=>"2012-01-01T00:00:00Z", "end_date"=>"2012-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Biochemistry", "average_usage"=>[316, 541, 663, 766, 856, 950, 1041, 1128, 1218, 1302, 1382, 1456, 1526, 1593, 1657, 1729, 1796, 1862, 1930, 1999, 2065, 2132, 2202, 2261, 2319]}, {"subject_area"=>"/Physical sciences", "average_usage"=>[304, 506, 616, 712, 799, 879, 968, 1052, 1134, 1212, 1284, 1357, 1427, 1494, 1557, 1621, 1689, 1756, 1823, 1883, 1944, 1997, 2056, 2118, 2171]}, {"subject_area"=>"/Physical sciences/Chemistry", "average_usage"=>[302, 508, 622, 720, 804, 888, 973, 1054, 1141, 1219, 1299, 1370, 1442, 1511, 1574, 1644, 1711, 1782, 1846, 1911, 1971, 2030, 2097, 2155, 2217]}, {"subject_area"=>"/Physical sciences/Physics", "average_usage"=>[298, 476, 578, 665, 743, 821, 891, 962, 1036, 1108, 1174, 1240, 1312, 1371, 1430, 1494, 1551, 1609, 1673, 1736, 1795, 1857, 1913, 1976, 2035]}]}
Loading … Spinner
There are currently no alerts