View source for 2naq


==3D NMR solution structure of NLRP3 PYD==
<StructureSection load='2naq' size='340' side='right'caption='[[2naq]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2naq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2NAQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2NAQ FirstGlance]. <br>
</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=2naq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2naq OCA], [https://pdbe.org/2naq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2naq RCSB], [https://www.ebi.ac.uk/pdbsum/2naq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2naq ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/NLRP3_HUMAN NLRP3_HUMAN] CINCA syndrome with NLRP3 mutations;Familial cold urticaria;Muckle-Wells syndrome. The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.  The disease is caused by mutations affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/NLRP3_HUMAN NLRP3_HUMAN] As the sensor component of the NLRP3 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 NLRP3, 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. Activation of NLRP3 inflammasome is also required for HMGB1 secretion (PubMed:22801494). The active cytokines and HMGB1 stimulate inflammatory responses. Inflammasomes can also induce pyroptosis, an inflammatory form of programmed cell death. Under resting conditions, NLRP3 is autoinhibited. NLRP3 activation stimuli include extracellular ATP, reactive oxygen species, K(+) efflux, crystals of monosodium urate or cholesterol, beta-amyloid fibers, environmental or industrial particles and nanoparticles, etc. However, it is unclear what constitutes the direct NLRP3 activator. Independently of inflammasome activation, regulates the differentiation of T helper 2 (Th2) cells and has a role in Th2 cell-dependent asthma and tumor growth (By similarity). During Th2 differentiation, required for optimal IRF4 binding to IL4 promoter and for IRF4-dependent IL4 transcription. Binds to the consensus DNA sequence 5'-GRRGGNRGAG-3'. May also participate in the transcription of IL5, IL13, GATA3, CCR3, CCR4 and MAF (By similarity).[UniProtKB:Q8R4B8]<ref>PMID:22801494</ref> <ref>PMID:23305783</ref> 
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== Publication Abstract from PubMed ==
Death Domain superfamily members typically act as adaptors mediating in the assembly of supramolecular complexes with critical apoptosis and inflammation functions. These modular proteins consist of death domains (DD), death effector domains (DED), caspase recruitment domains (CARD) and pyrin domains (PYD). Despite the high structural similarity amongst them only homotypic interactions participate in complex formation, suggesting that subtle factors differentiate each interaction type. It is thus critical to identify these factors as an essential step towards the understanding of the molecular basis of apoptosis and inflammation. The proteins ASC and NLRP3 play key roles in the regulation of apoptosis and inflammation through self-association and protein-protein interactions mediated by their PYDs. To better understand the molecular basis of their function we have characterized ASC and NLRP3 PYD self-association and their intermolecular interaction by solution NMR spectroscopy and analytical ultracentrifugation. We found that ASC self-associates and binds NLRP3 PYD through equivalent protein regions, with higher binding affinity for the latter. These regions are located in opposite sides of the protein allowing multimeric complex formation previously shown in ASC PYD fibril assemblies. We show that NLRP3 PYD coexists in solution as monomer and high-populated large-order oligomerized species. In spite of which, we determined its monomeric 3D solution structure by NMR and characterized its binding to ASC PYD. Using our novel structural data we propose molecular models of ASC-ASC and ASC-NLRP3 PYD early supramolecular complexes, providing new insights into the molecular mechanisms of inflammasome and apoptosis signaling.

Asc Pyrin Domain Self-Associates and Binds Nlrp3 Using Equivalent Binding Interfaces.,Oroz J, Barrera-Vilarmau S, Alfonso C, Rivas G, de Alba E J Biol Chem. 2016 Jul 18. pii: jbc.M116.741082. PMID:27432880<ref>PMID:27432880</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 2naq" style="background-color:#fffaf0;"></div>

==See Also==
*[[Pyrin domain|Pyrin domain]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Oroz J]]
[[Category: De Alba E]]