4bj3
Integrin alpha2 I domain E318W-collagen complex
Structural highlights
FunctionITA2_HUMAN Integrin alpha-2/beta-1 is a receptor for laminin, collagen, collagen C-propeptides, fibronectin and E-cadherin. It recognizes the proline-hydroxylated sequence G-F-P-G-E-R in collagen. It is responsible for adhesion of platelets and other cells to collagens, modulation of collagen and collagenase gene expression, force generation and organization of newly synthesized extracellular matrix. Publication Abstract from PubMedThe 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 alpha2beta1 I domain displays a relaxed collagen specificity, typical of an active state. E318W binds more strongly than the wild-type alpha2 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. An activating mutation reveals a second binding mode of the integrin alpha2 I domain to the GFOGER motif in collagens.,Carafoli F, Hamaia SW, Bihan D, Hohenester E, Farndale RW PLoS One. 2013 Jul 29;8(7):e69833. doi: 10.1371/journal.pone.0069833. Print 2013. PMID:23922814[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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