PDBsum entry 4bj3

Cell adhesion

PDB id: 4bj3

Contents

Protein chains

183 a.a.

18 a.a.

Ligands

BTB

Metals

_MG ×2

_CL

PDB id:

4bj3

Name:

Cell adhesion

Title:

Integrin alpha2 i domain e318w-collagen complex

Structure:

Integrin alpha-2. Chain: a, b. Fragment: i domain, residues 171-368. Synonym: cd49 antigen-like family member b, collagen receptor, platelet membrane glycoprotein ia, gpia, vla-2 subunit alpha, cd49b. Engineered: yes. Mutation: yes. Gfoger peptide. Chain: c, d, e.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 469008. Expression_system_variant: origami. Synthetic: yes. Organism_taxid: 9606

Resolution:

3.04Å R-factor: 0.251 R-free: 0.298

Authors:

F.Carafoli,S.W.Hamaia,D.Bihan,E.Hohenester,R.W.Farndale

Key ref:

F.Carafoli et al. (2013). An activating mutation reveals a second binding mode of the integrin α2 I domain to the GFOGER motif in collagens. Plos One, 8, e69833. PubMed id: 23922814 DOI: 10.1371/journal.pone.0069833

Date:

16-Apr-13 Release date: 20-Nov-13

Protein chains

P17301  (ITA2_HUMAN) -  Integrin alpha-2 from Homo sapiens

Seq: 1181 a.a.

Struc: 183 a.a.*

Protein chains

Q96A83  (COQA1_HUMAN) -  Collagen alpha-1(XXVI) chain from Homo sapiens

Seq: 441 a.a.

Struc: 18 a.a.*

* PDB and UniProt seqs differ at 8 residue positions (black crosses)

DOI no: 10.1371/journal.pone.0069833

Plos One 8:e69833 (2013)

PubMed id: 23922814

An activating mutation reveals a second binding mode of the integrin α2 I domain to the GFOGER motif in collagens.

F.Carafoli, S.W.Hamaia, D.Bihan, E.Hohenester, R.W.Farndale.

ABSTRACT

The GFOGER motif in collagens (O denotes hydroxyproline) represents a high-affinity binding site for all collagen-binding integrins. Other GxOGER motifs require integrin activation for maximal binding. The E318W mutant of the integrin α2β1 I domain displays a relaxed collagen specificity, typical of an active state. E318W binds more strongly than the wild-type α2 I domain to GMOGER, and forms a 2:1 complex with a homotrimeric, collagen-like, GFOGER peptide. Crystal structure analysis of this complex reveals two E318W I domains, A and B, bound to a single triple helix. The E318W I domains are virtually identical to the collagen-bound wild-type I domain, suggesting that the E318W mutation activates the I domain by destabilising the unligated conformation. E318W I domain A interacts with two collagen chains similarly to wild-type I domain (high-affinity mode). E318W I domain B makes favourable interactions with only one collagen chain (low-affinity mode). This observation suggests that single GxOGER motifs in the heterotrimeric collagens V and IX may support binding of activated integrins.