Functional and Evolutionary Analyses Identify Proteolysis as a General Mechanism for NLRP1 Inflammasome Activation
Publication Date
December 07, 2016
Authors
Joseph Chavarría Smith, Patrick S. Mitchell, Alvin M. Ho, Matthew D. Daugherty, et al
Volume
12
Issue
12
Pages
e1006052
DOI
http://doi.org/10.1371/journal.ppat.1006052
Publisher URL
http://journals.plos.org/plospathogens/article?id=10.1371%2Fjournal.ppat.1006052
Scopus
85007583900
Mendeley
http://www.mendeley.com/research/functional-evolutionary-analyses-identify-proteolysis-general-mechanism-nlrp1-inflammasome-activatio-1
Events
Loading … Spinner

Mendeley | Further Information

{"title"=>"Functional and Evolutionary Analyses Identify Proteolysis as a General Mechanism for NLRP1 Inflammasome Activation", "type"=>"journal", "authors"=>[{"first_name"=>"Joseph", "last_name"=>"Chavarría-Smith", "scopus_author_id"=>"41260901900"}, {"first_name"=>"Patrick S.", "last_name"=>"Mitchell", "scopus_author_id"=>"36011992700"}, {"first_name"=>"Alvin M.", "last_name"=>"Ho", "scopus_author_id"=>"57192720926"}, {"first_name"=>"Matthew D.", "last_name"=>"Daugherty", "scopus_author_id"=>"7006558242"}, {"first_name"=>"Russell E.", "last_name"=>"Vance", "scopus_author_id"=>"7103176370"}], "year"=>2016, "source"=>"PLoS Pathogens", "identifiers"=>{"issn"=>"15537374", "doi"=>"10.1371/journal.ppat.1006052", "sgr"=>"85007583900", "scopus"=>"2-s2.0-85007583900", "pmid"=>"27926929", "pui"=>"613937808"}, "id"=>"7cfae375-055c-3e0e-bc56-d11069608690", "abstract"=>"Inflammasomes are cytosolic multi-protein complexes that initiate immune responses to infection by recruiting and activating the Caspase-1 protease. Human NLRP1 was the first protein shown to form an inflammasome, but its physiological mechanism of activation remains unknown. Recently, specific variants of mouse and rat NLRP1 were found to be activated upon N-terminal cleavage by the anthrax lethal factor protease. However, agonists for other NLRP1 variants, including human NLRP1, are not known, and it remains unclear if they are also activated by proteolysis. Here we demonstrate that two mouse NLRP1 paralogs (NLRP1AB6 and NLRP1BB6) are also activated by N-terminal proteolytic cleavage. We also demonstrate that proteolysis within a specific N-terminal linker region is sufficient to activate human NLRP1. Evolutionary analysis of primate NLRP1 shows the linker/cleavage region has evolved under positive selection, indicative of pathogen-induced selective pressure. Collectively, these results identify proteolysis as a general mechanism of NLRP1 inflammasome activation that appears to be contributing to the rapid evolution of NLRP1 in rodents and primates.", "link"=>"http://www.mendeley.com/research/functional-evolutionary-analyses-identify-proteolysis-general-mechanism-nlrp1-inflammasome-activatio-1", "reader_count"=>22, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Other"=>2, "Student > Master"=>2, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>3, "Student > Doctoral Student"=>1, "Student > Ph. D. Student"=>9, "Other"=>2, "Student > Master"=>2, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>4, "Medicine and Dentistry"=>1, "Agricultural and Biological Sciences"=>5, "Neuroscience"=>1, "Immunology and Microbiology"=>10, "Engineering"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>1}, "Neuroscience"=>{"Neuroscience"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>10}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}}, "group_count"=>1}

Scopus | Further Information

{"@_fa"=>"true", "link"=>[{"@_fa"=>"true", "@ref"=>"self", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/85007583900"}, {"@_fa"=>"true", "@ref"=>"author-affiliation", "@href"=>"https://api.elsevier.com/content/abstract/scopus_id/85007583900?field=author,affiliation"}, {"@_fa"=>"true", "@ref"=>"scopus", "@href"=>"https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85007583900&origin=inward"}, {"@_fa"=>"true", "@ref"=>"scopus-citedby", "@href"=>"https://www.scopus.com/inward/citedby.uri?partnerID=HzOxMe3b&scp=85007583900&origin=inward"}], "prism:url"=>"https://api.elsevier.com/content/abstract/scopus_id/85007583900", "dc:identifier"=>"SCOPUS_ID:85007583900", "eid"=>"2-s2.0-85007583900", "dc:title"=>"Functional and Evolutionary Analyses Identify Proteolysis as a General Mechanism for NLRP1 Inflammasome Activation", "dc:creator"=>"Chavarría-Smith J.", "prism:publicationName"=>"PLoS Pathogens", "prism:issn"=>"15537366", "prism:eIssn"=>"15537374", "prism:volume"=>"12", "prism:issueIdentifier"=>"12", "prism:pageRange"=>nil, "prism:coverDate"=>"2016-12-07", "prism:coverDisplayDate"=>"7 December 2016", "prism:doi"=>"10.1371/journal.ppat.1006052", "citedby-count"=>"17", "affiliation"=>[{"@_fa"=>"true", "affilname"=>"University of California, Berkeley", "affiliation-city"=>"Berkeley", "affiliation-country"=>"United States"}], "pubmed-id"=>"27926929", "prism:aggregationType"=>"Journal", "subtype"=>"ar", "subtypeDescription"=>"Article", "article-number"=>"e1006052", "source-id"=>"4000151809", "openaccess"=>"1", "openaccessFlag"=>true}

Counter

  • {"month"=>"12", "year"=>"2016", "pdf_views"=>"125", "xml_views"=>"25", "html_views"=>"902"}
  • {"month"=>"1", "year"=>"2017", "pdf_views"=>"74", "xml_views"=>"3", "html_views"=>"190"}
  • {"month"=>"2", "year"=>"2017", "pdf_views"=>"44", "xml_views"=>"1", "html_views"=>"100"}
  • {"month"=>"3", "year"=>"2017", "pdf_views"=>"20", "xml_views"=>"1", "html_views"=>"85"}
  • {"month"=>"4", "year"=>"2017", "pdf_views"=>"18", "xml_views"=>"2", "html_views"=>"66"}
  • {"month"=>"5", "year"=>"2017", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"62"}
  • {"month"=>"6", "year"=>"2017", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"97"}
  • {"month"=>"7", "year"=>"2017", "pdf_views"=>"16", "xml_views"=>"0", "html_views"=>"58"}
  • {"month"=>"8", "year"=>"2017", "pdf_views"=>"22", "xml_views"=>"1", "html_views"=>"84"}
  • {"month"=>"9", "year"=>"2017", "pdf_views"=>"11", "xml_views"=>"2", "html_views"=>"29"}
  • {"month"=>"10", "year"=>"2017", "pdf_views"=>"19", "xml_views"=>"0", "html_views"=>"58"}
  • {"month"=>"11", "year"=>"2017", "pdf_views"=>"13", "xml_views"=>"0", "html_views"=>"79"}
  • {"month"=>"12", "year"=>"2017", "pdf_views"=>"8", "xml_views"=>"0", "html_views"=>"42"}
  • {"month"=>"1", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"2", "year"=>"2018", "pdf_views"=>"21", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"3", "year"=>"2018", "pdf_views"=>"19", "xml_views"=>"1", "html_views"=>"49"}
  • {"month"=>"4", "year"=>"2018", "pdf_views"=>"15", "xml_views"=>"1", "html_views"=>"52"}
  • {"month"=>"5", "year"=>"2018", "pdf_views"=>"15", "xml_views"=>"0", "html_views"=>"35"}
  • {"month"=>"6", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"39"}
  • {"month"=>"7", "year"=>"2018", "pdf_views"=>"5", "xml_views"=>"3", "html_views"=>"17"}
  • {"month"=>"8", "year"=>"2018", "pdf_views"=>"8", "xml_views"=>"1", "html_views"=>"28"}
  • {"month"=>"9", "year"=>"2018", "pdf_views"=>"9", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"10", "year"=>"2018", "pdf_views"=>"18", "xml_views"=>"0", "html_views"=>"31"}
  • {"month"=>"11", "year"=>"2018", "pdf_views"=>"26", "xml_views"=>"0", "html_views"=>"40"}
  • {"month"=>"12", "year"=>"2018", "pdf_views"=>"6", "xml_views"=>"0", "html_views"=>"16"}
  • {"month"=>"1", "year"=>"2019", "pdf_views"=>"1", "xml_views"=>"0", "html_views"=>"19"}

PMC Usage Stats

  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2016", "month"=>"12"}
  • {"unique-ip"=>"39", "full-text"=>"33", "pdf"=>"13", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"17", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"1"}
  • {"unique-ip"=>"26", "full-text"=>"22", "pdf"=>"11", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"6", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2017", "month"=>"2"}
  • {"unique-ip"=>"34", "full-text"=>"29", "pdf"=>"9", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"16", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"3"}
  • {"unique-ip"=>"17", "full-text"=>"14", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"7", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"4"}
  • {"unique-ip"=>"23", "full-text"=>"22", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"12", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2017", "month"=>"5"}
  • {"unique-ip"=>"11", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"8", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2017", "month"=>"6"}
  • {"unique-ip"=>"17", "full-text"=>"16", "pdf"=>"5", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"3", "cited-by"=>"0", "year"=>"2017", "month"=>"7"}
  • {"unique-ip"=>"12", "full-text"=>"16", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"11", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"8"}
  • {"unique-ip"=>"17", "full-text"=>"13", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"5", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"9"}
  • {"unique-ip"=>"14", "full-text"=>"15", "pdf"=>"6", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"10"}
  • {"unique-ip"=>"14", "full-text"=>"14", "pdf"=>"4", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"11"}
  • {"unique-ip"=>"10", "full-text"=>"9", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2017", "month"=>"12"}
  • {"unique-ip"=>"8", "full-text"=>"8", "pdf"=>"2", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"1"}
  • {"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"=>"2018", "month"=>"2"}
  • {"unique-ip"=>"19", "full-text"=>"16", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"3", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"3"}
Loading … Spinner
There are currently no alerts