This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
6drp
From Proteopedia
(Difference between revisions)
| Line 3: | Line 3: | ||
<StructureSection load='6drp' size='340' side='right' caption='[[6drp]], [[Resolution|resolution]] 3.58Å' scene=''> | <StructureSection load='6drp' size='340' side='right' caption='[[6drp]], [[Resolution|resolution]] 3.58Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6drp]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DRP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DRP FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6drp]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6DRP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6DRP FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6drp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6drp OCA], [http://pdbe.org/6drp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6drp RCSB], [http://www.ebi.ac.uk/pdbsum/6drp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6drp ProSAT]</span></td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NLRC4, CARD12, CLAN, CLAN1, IPAF, UNQ6189/PRO20215 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> |
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6drp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6drp OCA], [http://pdbe.org/6drp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6drp RCSB], [http://www.ebi.ac.uk/pdbsum/6drp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6drp ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
| Line 10: | Line 11: | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/NLRC4_HUMAN NLRC4_HUMAN]] Key component of inflammasomes that indirectly senses specific proteins from pathogenic bacteria and fungi and responds by assembling an inflammasome complex that promotes caspase-1 activation, cytokine production and macrophage pyroptosis (PubMed:15107016). The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria (By similarity).[UniProtKB:Q3UP24]<ref>PMID:15107016</ref> | [[http://www.uniprot.org/uniprot/NLRC4_HUMAN NLRC4_HUMAN]] Key component of inflammasomes that indirectly senses specific proteins from pathogenic bacteria and fungi and responds by assembling an inflammasome complex that promotes caspase-1 activation, cytokine production and macrophage pyroptosis (PubMed:15107016). The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria (By similarity).[UniProtKB:Q3UP24]<ref>PMID:15107016</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Canonical inflammasomes are cytosolic supramolecular complexes that activate caspase-1 upon sensing extrinsic microbial invasions and intrinsic sterile stress signals. During inflammasome assembly, adaptor proteins ASC and NLRC4 recruit caspase-1 through homotypic caspase recruitment domain (CARD) interactions, leading to caspase-1 dimerization and activation. Activated caspase-1 processes proinflammatory cytokines and Gasdermin D to induce cytokine maturation and pyroptotic cell death. Here, we present cryo-electron microscopy (cryo-EM) structures of NLRC4 CARD and ASC CARD filaments mediated by conserved three types of asymmetric interactions (types I, II, and III). We find that the CARDs of these two adaptor proteins share a similar assembly pattern, which matches that of the caspase-1 CARD filament whose structure we defined previously. These data indicate a unified mechanism for downstream caspase-1 recruitment through CARD-CARD interactions by both adaptors. Using structure modeling, we further show that full-length NLRC4 assembles via two separate symmetries at its CARD and its nucleotide-binding domain (NBD), respectively. | ||
| + | |||
| + | Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1.,Li Y, Fu TM, Lu A, Witt K, Ruan J, Shen C, Wu H Proc Natl Acad Sci U S A. 2018 Oct 2. pii: 1810524115. doi:, 10.1073/pnas.1810524115. PMID:30279182<ref>PMID:30279182</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6drp" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Fu, T]] | [[Category: Fu, T]] | ||
[[Category: Li, Y]] | [[Category: Li, Y]] | ||
Revision as of 08:37, 17 October 2018
Cryo-EM Structures of ASC and NLRC4 CARD Filaments Reveal a Unified Mechanism of Nucleation and Activation of Caspase-1
| |||||||||||
Categories: Human | Fu, T | Li, Y | Wu, H | Complex | Filament | Immune system | Innate immunity | Signaling
