View source for 9ihn


==Cryo-EM structure of NLRP3 bound to the inhibitor BAL-1516 at 3.06 Ang resolution==
<StructureSection load='9ihn' size='340' side='right'caption='[[9ihn]], [[Resolution|resolution]] 3.06&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9ihn]] is a 1 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=9IHN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9IHN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.06&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1I4G:3-ethoxy-~{N}-methyl-~{N}-[(1~{R})-1-(4-methyl-1~{H}-pyrazolo[4,3-c]pyridin-7-yl)ethyl]-4-(4-methyl-1,3-thiazol-2-yl)benzamide'>A1I4G</scene>, <scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></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=9ihn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9ihn OCA], [https://pdbe.org/9ihn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9ihn RCSB], [https://www.ebi.ac.uk/pdbsum/9ihn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9ihn 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> 
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Geyer M]]
[[Category: Hagelueken G]]
[[Category: Hartman G]]
[[Category: Torp J]]
[[Category: Wilhelmsen K]]