View source for 7lfh


==Cryo-EM structure of NLRP3 double-ring cage, 6-fold (12-mer)==
<StructureSection load='7lfh' size='340' side='right'caption='[[7lfh]], [[Resolution|resolution]] 4.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7LFH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LFH 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]] 4.2&#8491;</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=7lfh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lfh OCA], [https://pdbe.org/7lfh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lfh RCSB], [https://www.ebi.ac.uk/pdbsum/7lfh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lfh ProSAT]</span></td></tr>
</table>
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== Publication Abstract from PubMed ==
The NACHT-, leucine-rich-repeat- (LRR), and pyrin domain-containing protein 3 (NLRP3) is emerging to be a critical intracellular inflammasome sensor of membrane integrity and a highly important clinical target against chronic inflammation. Here, we report that an endogenous, stimulus-responsive form of full-length mouse NLRP3 is a 12- to 16-mer double-ring cage held together by LRR-LRR interactions with the pyrin domains shielded within the assembly to avoid premature activation. Surprisingly, this NLRP3 form is predominantly membrane localized, which is consistent with previously noted localization of NLRP3 at various membrane organelles. Structure-guided mutagenesis reveals that trans-Golgi network dispersion into vesicles, an early event observed for many NLRP3-activating stimuli, requires the double-ring cages of NLRP3. Double-ring-defective NLRP3 mutants abolish inflammasome punctum formation, caspase-1 processing, and cell death. Thus, our data uncover a physiological NLRP3 oligomer on the membrane that is poised to sense diverse signals to induce inflammasome activation.

NLRP3 cages revealed by full-length mouse NLRP3 structure control pathway activation.,Andreeva L, David L, Rawson S, Shen C, Pasricha T, Pelegrin P, Wu H Cell. 2021 Nov 30. pii: S0092-8674(21)01326-X. doi: 10.1016/j.cell.2021.11.011. PMID:34861190<ref>PMID:34861190</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 7lfh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Pyrin domain|Pyrin domain]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Andreeva L]]
[[Category: Rawson S]]
[[Category: Wu H]]