7vtq

<table><tr><td colspan='2'>[[7vtq]] is a 12 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VTQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VTQ FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7YN:1-[4-(2-oxidanylpropan-2-yl)furan-2-yl]sulfonyl-3-(1,2,3,5-tetrahydro-s-indacen-4-yl)urea'>7YN</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene></td></tr>

== Function ==

[[https://www.uniprot.org/uniprot/NLRP3_MOUSE NLRP3_MOUSE]] 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 (or possibly CASP4/CASP11). Recruitment of proCASP1 to the inflammasome promotes its activation and CASP1-catalyzed IL1B and IL18 maturation and secretion in the extracellular milieu (PubMed:28847925, PubMed:27374331). 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, amyloid-beta fibers, environmental or industrial particles and nanoparticles, cytosolic dsRNA, etc. However, it is unclear what constitutes the direct NLRP3 activator. Activation in presence of cytosolic dsRNA is mediated by DHX33 (By similarity). 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. 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 (PubMed:26098997).[UniProtKB:Q96P20]<ref>PMID:16407888</ref> <ref>PMID:16407890</ref> <ref>PMID:16546100</ref> <ref>PMID:17008311</ref> <ref>PMID:22801494</ref> <ref>PMID:26098997</ref> <ref>PMID:27374331</ref> <ref>PMID:28847925</ref>

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== Publication Abstract from PubMed ==

SignificanceThe nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) is a pattern recognition receptor that forms an inflammasome. The cryo-electron microscopy structure of the dodecameric form of full-length NLRP3 bound to the clinically relevant NLRP3-specific inhibitor MCC950 has established the structural basis for the oligomerization-mediated regulation of NLRP3 inflammasome activation and the mechanism of action of the NLRP3 specific inhibitor. The inactive NLRP3 oligomer represents the NLRP3 resting state, capable of binding to membranes and is likely disrupted for its activation. Visualization of the inhibitor binding mode will enable optimization of the activity of NLRP3 inflammasome inhibitor drugs.

Structural basis for the oligomerization-mediated regulation of NLRP3 inflammasome activation.,Ohto U, Kamitsukasa Y, Ishida H, Zhang Z, Murakami K, Hirama C, Maekawa S, Shimizu T Proc Natl Acad Sci U S A. 2022 Mar 15;119(11):e2121353119. doi:, 10.1073/pnas.2121353119. Epub 2022 Mar 7. PMID:35254907<ref>PMID:35254907</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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== References ==

<references/>

[[Category: Ohto, U]]

[[Category: Shimizu, T]]

[[Category: Nod-like receptor]]