PDBsum entry 5irn

Immune system

PDB id: 5irn

Contents

Protein chain

746 a.a.

Ligands

ADP

Waters ×47

PDB id:

5irn

Name:

Immune system

Title:

Crystal structure of rabbit nod2 in an adp-bound state (crystal form1)

Structure:

Uncharacterized protein. Chain: a. Fragment: unp residues 194-1020. Synonym: nod2. Engineered: yes

Source:

Oryctolagus cuniculus. Rabbit. Organism_taxid: 9986. Gene: nod2. Expressed in: spodoptera frugiperda. Expression_system_taxid: 7108.

Resolution:

2.34Å R-factor: 0.203 R-free: 0.236

Authors:

S.Maekawa,U.Ohto,T.Shimizu

Key ref:

S.Maekawa et al. (2016). Crystal structure of NOD2 and its implications in human disease. Nat Commun, 7, 11813. PubMed id: 27283905 DOI: 10.1038/ncomms11813

Date:

14-Mar-16 Release date: 29-Jun-16

Protein chain

G1T469  (G1T469_RABIT) -  Nucleotide-binding oligomerization domain-containing protein 2 from Oryctolagus cuniculus

Seq: 1013 a.a.

Struc: 746 a.a.

DOI no: 10.1038/ncomms11813

Nat Commun 7:11813 (2016)

PubMed id: 27283905

Crystal structure of NOD2 and its implications in human disease.

S.Maekawa, U.Ohto, T.Shibata, K.Miyake, T.Shimizu.

ABSTRACT

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.