OCA at 10:11, 14 December 2022

OCA — Wed, 14 Dec 2022 10:11:44 GMT

←Older revision		Revision as of 10:11, 14 December 2022
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-	'''Unreleased structure'''

-	The entry ~~8ert~~ is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==NLRP3 PYD filament==
		+	<StructureSection load='8ert' size='340' side='right'caption='[[8ert]], [[Resolution\|resolution]] 3.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[8ert]] 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=8ERT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ERT 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=8ert FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ert OCA], [https://pdbe.org/8ert PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ert RCSB], [https://www.ebi.ac.uk/pdbsum/8ert PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ert 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>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Inflammasomes are cytosolic innate immune complexes that activate caspase-1 upon detection of pathogenic and endogenous dangers(1-5), and NLRP3 is an inflammasome sensor of membrane damage highly important in inducing inflammation(2,6,7). Here we report cryo-EM structures of disk-shaped active NLRP3 oligomers in complex with ATP𝛾S, the centrosomal kinase NEK7, and the adaptor protein ASC which recruits caspase-1. In these NLRP3-NEK7-ASC complexes, the central NACHT domain of NLRP3 assumes an ATP-bound conformation in which two of its subdomains rotate by ~85 degrees relative to the ADP-bound inactive conformation(8-12). The FISNA domain conserved in NLRP3 but absent in most NLRPs(13) becomes ordered in its key regions to stabilize the active NACHT conformation and mediate most interactions in the disk. Mutations on these interactions compromise NLRP3-mediated caspase-1 activation. The N-terminal PYDs from all the NLRP3 subunits gather together to form a PYD filament that recruits ASC PYD to elicit downstream signalling. Surprisingly, the C-terminal LRR domain and the LRR-bound NEK7 do not participate in disk interfaces. Together with previous structures of inactive NLRP3 cage in which LRR-LRR interactions play an important role(8-11), we propose that the role of NEK7 is to break the inactive cage to transform NLRP3 into the active NLRP3 inflammasome disk.

-	~~Authors~~:	+	Cryo-EM structures of the active NLRP3 inflammasome disk.,Xiao L, Magupalli VG, Wu H Nature. 2022 Nov 28. doi: 10.1038/s41586-022-05570-8. PMID:36442502<ref>PMID:36442502</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
		+	<div class="pdbe-citations 8ert" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Homo sapiens]]
		+	[[Category: Large Structures]]
		+	[[Category: Wu H]]
		+	[[Category: Xiao L]]

OCA at 18:07, 16 November 2022

OCA — Wed, 16 Nov 2022 18:07:51 GMT

←Older revision		Revision as of 18:07, 16 November 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 8ert is ON HOLD	+	The entry 8ert is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "8ert" [edit=sysop:move=sysop]

OCA — Wed, 19 Oct 2022 17:30:47 GMT

Protected "8ert" [edit=sysop:move=sysop]

←Older revision

Revision as of 17:30, 19 October 2022

OCA: New page: '''Unreleased structure''' The entry 8ert is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 19 Oct 2022 17:30:46 GMT

New page: '''Unreleased structure''' The entry 8ert is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 8ert is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

8ert - Revision history

OCA at 10:11, 14 December 2022

OCA at 18:07, 16 November 2022

OCA: Protected "8ert" [edit=sysop:move=sysop]

OCA: New page: '''Unreleased structure''' The entry 8ert is ON HOLD Authors: Description: Category: Unreleased Structures