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| | <SX load='6ncv' size='340' side='right' viewer='molstar' caption='[[6ncv]], [[Resolution|resolution]] 3.70Å' scene=''> | | <SX load='6ncv' size='340' side='right' viewer='molstar' caption='[[6ncv]], [[Resolution|resolution]] 3.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6ncv]] is a 21 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=6NCV OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6NCV FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6ncv]] is a 21 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6NCV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6NCV FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NLRP6, NALP6, PYPAF5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.7Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6ncv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ncv OCA], [http://pdbe.org/6ncv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6ncv RCSB], [http://www.ebi.ac.uk/pdbsum/6ncv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6ncv ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6ncv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ncv OCA], [https://pdbe.org/6ncv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ncv RCSB], [https://www.ebi.ac.uk/pdbsum/6ncv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ncv ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/NLRP6_HUMAN NLRP6_HUMAN]] As the sensor component of the NLRP6 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP6, PYCARD and CASP1 (and possibly CASP4 and CASP5). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. The precise NLRP6 activation stimulus has not been identified yet (By similarity) (PubMed:12387869). Essential for gut mucosal self-renewal and proliferation. Maintains intestinal homeostasis and a healthy intestinal microbiota. This function is, at least partially, mediated by IL18, and not IL1B, produced by nonhematopoietic cells. Influences intestinal barrier function and microbial homeostasis through the regulation of goblet cell mucus secretion. Acts by promoting autophagy in goblet cells, an essential step for mucus granule exocytosis. Its role in goblet cell physiology is inflammasome-dependent, but IL1B- and IL18-independent. During systemic bacterial infections, may negatively regulate inflammatory signaling and inhibit the influx of monocytes and neutrophils to the circulation and to the peritoneum. May promote peripheral nerve recovery following injury via an inflammasome-independent mechanism (By similarity).[UniProtKB:Q91WS2][UniProtKB:Q96P20]<ref>PMID:12387869</ref> | + | [https://www.uniprot.org/uniprot/NLRP6_HUMAN NLRP6_HUMAN] As the sensor component of the NLRP6 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP6, PYCARD and CASP1 (and possibly CASP4 and CASP5). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. The precise NLRP6 activation stimulus has not been identified yet (By similarity) (PubMed:12387869). Essential for gut mucosal self-renewal and proliferation. Maintains intestinal homeostasis and a healthy intestinal microbiota. This function is, at least partially, mediated by IL18, and not IL1B, produced by nonhematopoietic cells. Influences intestinal barrier function and microbial homeostasis through the regulation of goblet cell mucus secretion. Acts by promoting autophagy in goblet cells, an essential step for mucus granule exocytosis. Its role in goblet cell physiology is inflammasome-dependent, but IL1B- and IL18-independent. During systemic bacterial infections, may negatively regulate inflammatory signaling and inhibit the influx of monocytes and neutrophils to the circulation and to the peritoneum. May promote peripheral nerve recovery following injury via an inflammasome-independent mechanism (By similarity).[UniProtKB:Q91WS2][UniProtKB:Q96P20]<ref>PMID:12387869</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Inflammasomes are large protein complexes that trigger host defense in cells by activating inflammatory caspases for cytokine maturation and pyroptosis. NLRP6 is a sensor protein in the nucleotide-binding domain (NBD) and leucine-rich repeat (LRR)-containing (NLR) inflammasome family that has been shown to play multiple roles in regulating inflammation and host defenses. Despite the significance of the NLRP6 inflammasome, little is known about the molecular mechanism behind its assembly and activation. Here we present cryo-EM and crystal structures of NLRP6 pyrin domain (PYD). We show that NLRP6 PYD alone is able to self-assemble into filamentous structures accompanied by large conformational changes and can recruit the ASC adaptor using PYD-PYD interactions. Using molecular dynamics simulations, we identify the surface that the NLRP6 PYD filament uses to recruit ASC PYD. We further find that full-length NLRP6 assembles in a concentration-dependent manner into wider filaments with a PYD core surrounded by the NBD and the LRR domain. These findings provide a structural understanding of inflammasome assembly by NLRP6 and other members of the NLR family.
| + | |
| | | | |
| - | Molecular mechanism for NLRP6 inflammasome assembly and activation.,Shen C, Lu A, Xie WJ, Ruan J, Negro R, Egelman EH, Fu TM, Wu H Proc Natl Acad Sci U S A. 2019 Feb 5;116(6):2052-2057. doi:, 10.1073/pnas.1817221116. Epub 2019 Jan 23. PMID:30674671<ref>PMID:30674671</ref>
| + | ==See Also== |
| - | | + | *[[Pyrin domain|Pyrin domain]] |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 6ncv" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Fu, T M]] | + | [[Category: Fu TM]] |
| - | [[Category: Shen, C]] | + | [[Category: Shen C]] |
| - | [[Category: Wu, H]] | + | [[Category: Wu H]] |
| - | [[Category: Death domain fold]]
| + | |
| - | [[Category: Helical assembly]]
| + | |
| - | [[Category: Inflammasome]]
| + | |
| - | [[Category: Protein fibril]]
| + | |
| - | [[Category: Signaling protein]]
| + | |
| Structural highlights
Function
NLRP6_HUMAN As the sensor component of the NLRP6 inflammasome, plays a crucial role in innate immunity and inflammation. In response to pathogens and other damage-associated signals, initiates the formation of the inflammasome polymeric complex, made of NLRP6, PYCARD and CASP1 (and possibly CASP4 and CASP5). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu. The precise NLRP6 activation stimulus has not been identified yet (By similarity) (PubMed:12387869). Essential for gut mucosal self-renewal and proliferation. Maintains intestinal homeostasis and a healthy intestinal microbiota. This function is, at least partially, mediated by IL18, and not IL1B, produced by nonhematopoietic cells. Influences intestinal barrier function and microbial homeostasis through the regulation of goblet cell mucus secretion. Acts by promoting autophagy in goblet cells, an essential step for mucus granule exocytosis. Its role in goblet cell physiology is inflammasome-dependent, but IL1B- and IL18-independent. During systemic bacterial infections, may negatively regulate inflammatory signaling and inhibit the influx of monocytes and neutrophils to the circulation and to the peritoneum. May promote peripheral nerve recovery following injury via an inflammasome-independent mechanism (By similarity).[UniProtKB:Q91WS2][UniProtKB:Q96P20][1]
See Also
References
- ↑ Grenier JM, Wang L, Manji GA, Huang WJ, Al-Garawi A, Kelly R, Carlson A, Merriam S, Lora JM, Briskin M, DiStefano PS, Bertin J. Functional screening of five PYPAF family members identifies PYPAF5 as a novel regulator of NF-kappaB and caspase-1. FEBS Lett. 2002 Oct 23;530(1-3):73-8. PMID:12387869
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