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PDBsum entry 5irl
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Immune system
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PDB id
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5irl
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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 nod2 and its implications in human disease.
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Authors
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S.Maekawa,
U.Ohto,
T.Shibata,
K.Miyake,
T.Shimizu.
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Ref.
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Nat Commun, 2016,
7,
11813.
[DOI no: ]
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PubMed id
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Abstract
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Nucleotide-binding oligomerization domain-containing protein 2 (NOD2), a member
of the NOD-like receptors family, are crucial for innate immune responses.
Mutations of NOD2 have been associated with chronic inflammatory disorders such
as Crohn's disease (CD), Blau syndrome (BS) and early-onset sarcoidosis (EOS),
but little is known about its signalling mechanism and the role it plays in
these diseases. Here, we report the crystal structure of rabbit NOD2 in an
ADP-bound state. The structure reveals an inactive closed conformation in which
the subdomains in the NOD domain are closely packed by ADP-mediated and
inter-domain interactions. Mapping of the BS- or EOS-associated gain-of-function
mutations reveals that most of these mutations are located in the NOD subdomain
interfaces, and are likely to disrupt the inner domain interactions,
facilitating a conformational change to the active form. Conversely, mutations
associated with CD are distributed throughout the protein, some of which may
affect oligomer formation and ligand binding.
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