3jbl
From Proteopedia
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| - | ''' | + | ==Cryo-EM Structure of the Activated NAIP2/NLRC4 Inflammasome Reveals Nucleated Polymerization== |
| + | <StructureSection load='3jbl' size='340' side='right' caption='[[3jbl]], [[Resolution|resolution]] 4.50Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[3jbl]] is a 11 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3JBL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3JBL FirstGlance]. <br> | ||
| + | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></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=3jbl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3jbl OCA], [http://pdbe.org/3jbl PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3jbl RCSB], [http://www.ebi.ac.uk/pdbsum/3jbl PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | {{Large structure}} | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/NLRC4_MOUSE NLRC4_MOUSE]] Key component of inflammasomes that indirectly senses specific proteins from pathogenic bacteria and fungi and responds by assembling an inflammasome complex that promotes caspase-1 activation, cytokine production and macrophage pyroptosis. The NLRC4 inflammasome is activated as part of the innate immune response to a range of intracellular bacteria. It senses pathogenic proteins of the type III secretion system (T3SS) and type IV secretion system (T4SS) such as flagellin and PrgJ-like rod proteins via the Naip proteins (Naip1, Naip2 or Naip5): specific Naip proteins recognize and bind pathogenic proteins, driving assembly and activation of the NLRC4 inflammasome. The NLRC4 inflammasome senses Gram-negative bacteria such as L.pneumophila and P.aeruginosa, enteric pathogens S.typhimurium (Salmonella) and S.flexneri and fungal pathogen C.albicans. In intestine, the NLRC4 inflammasome is able to discriminate between commensal and pathogenic bacteria and specifically drives production of interleukin-1 beta (IL1B) in response to infection by Salmonella or P.aeruginosa. In case of L.pneumophila infection the inflammasome acts by activating caspase-7.<ref>PMID:15190255</ref> <ref>PMID:16648853</ref> <ref>PMID:16648852</ref> <ref>PMID:18070936</ref> <ref>PMID:19343209</ref> <ref>PMID:20603313</ref> <ref>PMID:20133635</ref> <ref>PMID:21874021</ref> <ref>PMID:21918512</ref> <ref>PMID:22174673</ref> <ref>PMID:22547706</ref> <ref>PMID:22231517</ref> <ref>PMID:22484733</ref> <ref>PMID:22885697</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The NLR family apoptosis inhibitory proteins (NAIPs) bind conserved bacterial ligands, like the bacterial rod protein PrgJ, and recruit the NLR family CARD-containing protein 4 (NLRC4) as the inflammasome adapter to activate innate immunity. Here we show that the PrgJ-NAIP2-NLRC4 inflammasome is assembled into multisubunit disk-like structures through a unidirectional ATPase polymerization, primed with a single PrgJ-activated NAIP2 per disk. Cryo-electron microscopy (cryo-EM) reconstruction at a subnanometer resolution revealed a ~90 degrees hinge rotation accompanying NLRC4 activation. Unlike in the related, heptameric Apaf-1 apoptosome in which each subunit needs to be conformationally activated by its ligand before assembly, a single PrgJ-activated NAIP2 initiates NLRC4 polymerization in a domino-like reaction to promote the disk assembly. These insights reveal the mechanism of signal amplification in NAIP/NLRC4 inflammasomes. | ||
| - | + | Cryo-EM structure of the activated NAIP2-NLRC4 inflammasome reveals nucleated polymerization.,Zhang L, Chen S, Ruan J, Wu J, Tong AB, Yin Q, Li Y, David L, Lu A, Wang WL, Marks C, Ouyang Q, Zhang X, Mao Y, Wu H Science. 2015 Oct 8. pii: aac5789. PMID:26449474<ref>PMID:26449474</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | + | </div> | |
| - | + | <div class="pdbe-citations 3jbl" style="background-color:#fffaf0;"></div> | |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Chen, S]] | ||
| + | [[Category: David, L]] | ||
| + | [[Category: Li, Y]] | ||
[[Category: Lu, A]] | [[Category: Lu, A]] | ||
| + | [[Category: Mao, Y]] | ||
[[Category: Marks, C]] | [[Category: Marks, C]] | ||
| - | [[Category: Tong, A.B]] | ||
| - | [[Category: Zhang, L]] | ||
| - | [[Category: Li, Y]] | ||
[[Category: Ouyang, Q]] | [[Category: Ouyang, Q]] | ||
| - | [[Category: | + | [[Category: Ruan, J]] |
| + | [[Category: Tong, A B]] | ||
| + | [[Category: Wang, W L]] | ||
| + | [[Category: Wu, H]] | ||
[[Category: Wu, J]] | [[Category: Wu, J]] | ||
| - | [[Category: Mao, Y]] | ||
| - | [[Category: Ruan, J]] | ||
| - | [[Category: Chen, S]] | ||
| - | [[Category: David, L]] | ||
[[Category: Yin, Q]] | [[Category: Yin, Q]] | ||
| - | [[Category: | + | [[Category: Zhang, L]] |
| - | [[Category: | + | [[Category: Zhang, X]] |
| + | [[Category: Immune system]] | ||
| + | [[Category: Inflammasome]] | ||
| + | [[Category: Naip2]] | ||
| + | [[Category: Nlrc4]] | ||
Revision as of 05:23, 22 October 2015
Cryo-EM Structure of the Activated NAIP2/NLRC4 Inflammasome Reveals Nucleated Polymerization
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