6b5b: Difference between revisions

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<SX load='6b5b' size='340' side='right' viewer='molstar' caption='[[6b5b]], [[Resolution|resolution]] 5.20&Aring;' scene=''>
<SX load='6b5b' size='340' side='right' viewer='molstar' caption='[[6b5b]], [[Resolution|resolution]] 5.20&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[6b5b]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_33152 Atcc 33152] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B5B OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6B5B FirstGlance]. <br>
<table><tr><td colspan='2'>[[6b5b]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Legionella_pneumophila Legionella pneumophila] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B5B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6B5B FirstGlance]. <br>
</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Naip5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), Nlrc4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice]), fliC ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=446 ATCC 33152])</td></tr>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 5.2&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6b5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b5b OCA], [http://pdbe.org/6b5b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b5b RCSB], [http://www.ebi.ac.uk/pdbsum/6b5b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b5b ProSAT]</span></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=6b5b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b5b OCA], [https://pdbe.org/6b5b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6b5b RCSB], [https://www.ebi.ac.uk/pdbsum/6b5b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6b5b ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://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>  [[http://www.uniprot.org/uniprot/G8UUW9_LEGPN G8UUW9_LEGPN]] Flagellin is the subunit protein which polymerizes to form the filaments of bacterial flagella.[RuleBase:RU362073] [[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> 
[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 ==
Robust innate immune detection of rapidly evolving pathogens is critical for host defense. Nucleotide-binding domain leucine-rich repeat (NLR) proteins function as cytosolic innate immune sensors in plants and animals. However, the structural basis for ligand-induced NLR activation has so far remained unknown. NAIP5 (NLR family, apoptosis inhibitory protein 5) binds the bacterial protein flagellin and assembles with NLRC4 to form a multiprotein complex called an inflammasome. Here we report the cryo-electron microscopy structure of the assembled ~1.4-megadalton flagellin-NAIP5-NLRC4 inflammasome, revealing how a ligand activates an NLR. Six distinct NAIP5 domains contact multiple conserved regions of flagellin, prying NAIP5 into an open and active conformation. We show that innate immune recognition of multiple ligand surfaces is a generalizable strategy that limits pathogen evolution and immune escape.
 
The structural basis of flagellin detection by NAIP5: A strategy to limit pathogen immune evasion.,Tenthorey JL, Haloupek N, Lopez-Blanco JR, Grob P, Adamson E, Hartenian E, Lind NA, Bourgeois NM, Chacon P, Nogales E, Vance RE Science. 2017 Nov 17;358(6365):888-893. doi: 10.1126/science.aao1140. PMID:29146805<ref>PMID:29146805</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6b5b" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
*[[Baculoviral IAP repeat-containing protein 3D structures|Baculoviral IAP repeat-containing protein 3D structures]]
*[[Flagellin 3D structures|Flagellin 3D structures]]
*[[Flagellin 3D structures|Flagellin 3D structures]]
== References ==
== References ==
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__TOC__
__TOC__
</SX>
</SX>
[[Category: Atcc 33152]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Lk3 transgenic mice]]
[[Category: Legionella pneumophila]]
[[Category: Adamson, E]]
[[Category: Mus musculus]]
[[Category: Bourgeois, N M]]
[[Category: Adamson E]]
[[Category: Chacon, P]]
[[Category: Bourgeois NM]]
[[Category: Grob, P]]
[[Category: Chacon P]]
[[Category: Haloupek, N]]
[[Category: Grob P]]
[[Category: Hartenian, E]]
[[Category: Haloupek N]]
[[Category: Lind, N A]]
[[Category: Hartenian E]]
[[Category: Lopez-Blanco, J R]]
[[Category: Lind NA]]
[[Category: Nogales, E]]
[[Category: Lopez-Blanco JR]]
[[Category: Tenthorey, J L]]
[[Category: Nogales E]]
[[Category: Vance, R E]]
[[Category: Tenthorey JL]]
[[Category: Immune system]]
[[Category: Vance RE]]
[[Category: Innate immunity]]
[[Category: Molecular complex]]

Latest revision as of 17:20, 13 March 2024

Cryo-EM structure of the NAIP5-NLRC4-flagellin inflammasomeCryo-EM structure of the NAIP5-NLRC4-flagellin inflammasome

6b5b, resolution 5.20Å

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