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2naq

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Revision as of 17:03, 15 August 2018

3D NMR solution structure of NLRP3 PYD

Structural highlights

2naq is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	NLRP3, C1orf7, CIAS1, NALP3, PYPAF1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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

[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]^[1] ^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lu B, Nakamura T, Inouye K, Li J, Tang Y, Lundback P, Valdes-Ferrer SI, Olofsson PS, Kalb T, Roth J, Zou Y, Erlandsson-Harris H, Yang H, Ting JP, Wang H, Andersson U, Antoine DJ, Chavan SS, Hotamisligil GS, Tracey KJ. Novel role of PKR in inflammasome activation and HMGB1 release. Nature. 2012 Aug 30;488(7413):670-4. doi: 10.1038/nature11290. PMID:22801494 doi:http://dx.doi.org/10.1038/nature11290
↑ Haneklaus M, O'Neill LA, Coll RC. Modulatory mechanisms controlling the NLRP3 inflammasome in inflammation: recent developments. Curr Opin Immunol. 2013 Feb;25(1):40-5. doi: 10.1016/j.coi.2012.12.004. Epub 2013, Jan 7. PMID:23305783 doi:http://dx.doi.org/10.1016/j.coi.2012.12.004
↑ Oroz J, Barrera-Vilarmau S, Alfonso C, Rivas G, de Alba E. Asc Pyrin Domain Self-Associates and Binds Nlrp3 Using Equivalent Binding Interfaces. J Biol Chem. 2016 Jul 18. pii: jbc.M116.741082. PMID:27432880 doi:http://dx.doi.org/10.1074/jbc.M116.741082

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2naq"

Categories: Human | Alba, E de | Oroz, J | Apoptosis | Death domain superfamily

@@ Line 3: / Line 3: @@
 <StructureSection load='2naq' size='340' side='right' caption='[[2naq]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2naq]] is a 1 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2NAQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2naq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://oca.weizmann.ac.il/oca-docs/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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2naq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2naq OCA], [http://pdbe.org/2naq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2naq RCSB], [http://www.ebi.ac.uk/pdbsum/2naq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2naq ProSAT]</span></td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NLRP3, C1orf7, CIAS1, NALP3, PYPAF1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2naq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2naq OCA], [http://pdbe.org/2naq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2naq RCSB], [http://www.ebi.ac.uk/pdbsum/2naq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2naq ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 </div>
 <div class="pdbe-citations 2naq" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Pyrin domain|Pyrin domain]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Alba, E de]]
 [[Category: Oroz, J]]
 [[Category: Apoptosis]]
 [[Category: Death domain superfamily]]

2naq

From Proteopedia

Revision as of 17:03, 15 August 2018

3D NMR solution structure of NLRP3 PYD

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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