5aj2
From Proteopedia
(Difference between revisions)
| (5 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
==Cryo electron tomography of the Naip5-Nlrc4 inflammasome== | ==Cryo electron tomography of the Naip5-Nlrc4 inflammasome== | ||
| - | < | + | <SX load='5aj2' size='340' side='right' viewer='molstar' caption='[[5aj2]], [[Resolution|resolution]] 40.00Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5aj2]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AJ2 OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5aj2]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5AJ2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5AJ2 FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 40Å</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=5aj2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5aj2 OCA], [https://pdbe.org/5aj2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5aj2 RCSB], [https://www.ebi.ac.uk/pdbsum/5aj2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5aj2 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://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 == | ||
| + | Inflammasomes are high molecular weight protein complexes that play a crucial role in innate immunity by activating caspase-1. Inflammasome formation is initiated when molecules originating from invading microorganisms activate nucleotide-binding domain and leucine-rich repeat-containing receptors (NLRs) and induce NLR multimerization. Little is known about the conformational changes involved in NLR activation and the structural organization of NLR multimers. Here, we show by cryoelectron tomography that flagellin-induced NAIP5/NLRC4 multimers form right- and left-handed helical polymers with a diameter of 28 nm and a pitch of 6.5 nm. Subtomogram averaging produced an electron density map at 4 nm resolution, which was used for rigid body fitting of NLR subdomains derived from the crystal structure of dormant NLRC4. The resulting structural model of inflammasome-incorporated NLRC4 indicates that a prominent rotation of the LRR domain of NLRC4 is necessary for multimer formation, providing unprecedented insight into the conformational changes that accompany NLR activation. | ||
| + | |||
| + | Cryoelectron Tomography of the NAIP5/NLRC4 Inflammasome: Implications for NLR Activation.,Diebolder CA, Halff EF, Koster AJ, Huizinga EG, Koning RI Structure. 2015 Dec 1;23(12):2349-57. doi: 10.1016/j.str.2015.10.001. Epub 2015, Nov 12. PMID:26585513<ref>PMID:26585513</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5aj2" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
| - | </ | + | </SX> |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Mus musculus]] |
| - | [[Category: | + | [[Category: Diebolder CA]] |
| - | [[Category: | + | [[Category: Halff EF]] |
| - | [[Category: | + | [[Category: Huizinga EG]] |
| - | [[Category: | + | [[Category: Koning RI]] |
| + | [[Category: Koster AJ]] | ||
Current revision
Cryo electron tomography of the Naip5-Nlrc4 inflammasome
| |||||||||
