View source for 7rav


==Cryo-EM structure of the unliganded form of NLR family apoptosis inhibitory protein 5 (NAIP5)==
<StructureSection load='7rav' size='340' side='right'caption='[[7rav]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7rav]] is a 1 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=7RAV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RAV 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]] 3.3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ATP:ADENOSINE-5-TRIPHOSPHATE'>ATP</scene></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=7rav FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rav OCA], [https://pdbe.org/7rav PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rav RCSB], [https://www.ebi.ac.uk/pdbsum/7rav PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rav ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BIR1E_MOUSE BIR1E_MOUSE] Sensor component of the NLRC4 inflammasome that specifically recognizes and binds flagellin from pathogenic bacteria such as Legionella or Salmonella. Association of pathogenic bacteria proteins drives in turn drive assembly and activation of the NLRC4 inflammasome, promoting 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. The NLRC4 inflammasome senses Gram-negative bacteria such as L.pneumophila and P.aeruginosa, enteric pathogens S.typhimurium (Salmonella) and S.flexneri. Prevents motor-neuron apoptosis induced by a variety of signals.<ref>PMID:21874021</ref> <ref>PMID:21918512</ref> 
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== Publication Abstract from PubMed ==
The nucleotide-binding domain (NBD), leucine rich repeat (LRR) domain containing protein family (NLR family) apoptosis inhibitory proteins (NAIPs) are cytosolic receptors that play critical roles in the host defense against bacterial infection. NAIPs interact with conserved bacterial ligands and activate the NLR family caspase recruitment domain containing protein 4 (NLRC4) to initiate the NAIP-NLRC4 inflammasome pathway. Here we found the process of NAIP activation is completely different from NLRC4. Our cryo-EM structure of unliganded mouse NAIP5 adopts an unprecedented wide-open conformation, with the nucleating surface fully exposed and accessible to recruit inactive NLRC4. Upon ligand binding, the winged helix domain (WHD) of NAIP5 undergoes roughly 20 degrees rotation to form a steric clash with the inactive NLRC4, which triggers the conformational change of NLRC4 from inactive to active state. We also show the rotation of WHD places the 17-18 loop at a position that directly bind the active NLRC4 and stabilize the NAIP5-NLRC4 complex. Overall, these data provide structural mechanisms of inactive NAIP5, the process of NAIP5 activation and NAIP-dependent NLRC4 activation.

Mechanism of NAIP-NLRC4 inflammasome activation revealed by cryo-EM structure of unliganded NAIP5.,Paidimuddala B, Cao J, Nash G, Xie Q, Wu H, Zhang L Nat Struct Mol Biol. 2023 Feb;30(2):159-166. doi: 10.1038/s41594-022-00889-2. , Epub 2023 Jan 5. PMID:36604500<ref>PMID:36604500</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 7rav" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Cao J]]
[[Category: Paidimuddala B]]
[[Category: Wu H]]
[[Category: Xie Q]]
[[Category: Zhang L]]