4kxf

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
{{Large structure}}
+
==Crystal structure of NLRC4 reveals its autoinhibition mechanism==
-
{{STRUCTURE_4kxf| PDB=4kxf | SCENE= }}
+
<StructureSection load='4kxf' size='340' side='right' caption='[[4kxf]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
-
===Crystal structure of NLRC4 reveals its autoinhibition mechanism===
+
== Structural highlights ==
-
{{ABSTRACT_PUBMED_23765277}}
+
<table><tr><td colspan='2'>[[4kxf]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KXF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4KXF FirstGlance]. <br>
 +
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Nlrc4, Card12, Ipaf ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</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=4kxf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4kxf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4kxf RCSB], [http://www.ebi.ac.uk/pdbsum/4kxf PDBsum]</span></td></tr>
 +
</table>
 +
<div style="background-color:#fffaf0;">
 +
== Publication Abstract from PubMed ==
 +
Nucleotide-binding and oligomerization domain-like receptor (NLR) proteins oligomerize into multiprotein complexes termed inflammasomes when activated. Their autoinhibition mechanism remains poorly defined. Here, we report the crystal structure of mouse NLRC4 in a closed form. The adenosine diphosphate-mediated interaction between the central nucleotide-binding domain (NBD) and the winged-helix domain (WHD) was critical for stabilizing the closed conformation of NLRC4. The helical domain HD2 repressively contacted a conserved and functionally important alpha-helix of the NBD. The C-terminal leucine-rich repeat (LRR) domain is positioned to sterically occlude one side of the NBD domain and consequently sequester NLRC4 in a monomeric state. Disruption of ADP-mediated NBD-WHD or NBD-HD2/NBD-LRR interactions resulted in constitutive activation of NLRC4. Together, our data reveal the NBD-organized cooperative autoinhibition mechanism of NLRC4 and provide insight into its activation.
-
==Function==
+
Crystal structure of NLRC4 reveals its autoinhibition mechanism.,Hu Z, Yan C, Liu P, Huang Z, Ma R, Zhang C, Wang R, Zhang Y, Martinon F, Miao D, Deng H, Wang J, Chang J, Chai J Science. 2013 Jul 12;341(6142):172-5. doi: 10.1126/science.1236381. Epub 2013 Jun, 13. PMID:23765277<ref>PMID:23765277</ref>
-
[[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>
+
-
==About this Structure==
+
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-
[[4kxf]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4KXF OCA].
+
</div>
-
 
+
== References ==
-
==Reference==
+
<references/>
-
<ref group="xtra">PMID:023765277</ref><references group="xtra"/><references/>
+
__TOC__
 +
</StructureSection>
[[Category: Mus musculus]]
[[Category: Mus musculus]]
-
[[Category: Chai, J.]]
+
[[Category: Chai, J]]
-
[[Category: Hu, Z.]]
+
[[Category: Hu, Z]]
[[Category: Adp binding]]
[[Category: Adp binding]]
[[Category: Auto-inhibition]]
[[Category: Auto-inhibition]]

Revision as of 15:09, 21 December 2014

Crystal structure of NLRC4 reveals its autoinhibition mechanism

4kxf, resolution 3.20Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4kxf"
Personal tools