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PDBsum entry 4kxf
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Immune system
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PDB id
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4kxf
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References listed in PDB file
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Key reference
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Title
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Crystal structure of nlrc4 reveals its autoinhibition mechanism.
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Authors
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Z.Hu,
C.Yan,
P.Liu,
Z.Huang,
R.Ma,
C.Zhang,
R.Wang,
Y.Zhang,
F.Martinon,
D.Miao,
H.Deng,
J.Wang,
J.Chang,
J.Chai.
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Ref.
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Science, 2013,
341,
172-175.
[DOI no: ]
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PubMed id
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Abstract
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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 α-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.
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