An Activating Mutation Reveals a Second Binding Mode of the Integrin alpha 2 I Domain to the GFOGER Motif in Collagens

作者：Carafoli Federico; Hamaia Samir W; Bihan Dominique; Hohenester Erhard; Farndale Richard W^*

来源：PLos One, 2013, 8(7): e69833.

DOI：10.1371/journal.pone.0069833

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 alpha 2b1 I domain displays a relaxed collagen specificity, typical of an active state. E318W binds more strongly than the wild-type alpha 2 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.

• 出版日期2013-7-29