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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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PDB id:
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Immune system
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Title:
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Crystal structure of nlrc4 reveals its autoinhibition mechanism
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Structure:
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Nlr family card domain-containing protein 4. Chain: k, b, d, f, h, l, n, p. Synonym: caspase recruitment domain-containing protein 12, ice protease-activating factor, ipaf. Engineered: yes
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Source:
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Mus musculus. Mouse. Organism_taxid: 10090. Gene: nlrc4, card12, ipaf. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108
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Resolution:
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3.20Å
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R-factor:
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0.228
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R-free:
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0.266
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Authors:
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J.Chai,Z.Hu
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Key ref:
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Z.Hu
et al.
(2013).
Crystal structure of NLRC4 reveals its autoinhibition mechanism.
Science,
341,
172-175.
PubMed id:
DOI:
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Date:
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25-May-13
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Release date:
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24-Jul-13
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PROCHECK
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Headers
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References
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Q3UP24
(NLRC4_MOUSE) -
NLR family CARD domain-containing protein 4 from Mus musculus
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Seq:
Struc:
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1024 a.a.
904 a.a.
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Key: |
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PfamA domain |
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Secondary structure |
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CATH domain |
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DOI no:
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Science
341:172-175
(2013)
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PubMed id:
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Crystal structure of NLRC4 reveals its autoinhibition mechanism.
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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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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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Links
