Open AccessAn Activating Mutation Reveals a Second Binding Mode of the Integrin α2 I Domain to the GFOGER Motif in Collagens
Author(s) -
Federico Carafoli,
Samir Hamaia,
Dominique Bihan,
Erhard Hohenester,
Richard W. Farndale
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0069833
Subject(s) - integrin , heterotrimeric g protein , mutant , collagen receptor , chemistry , binding site , plasma protein binding , type i collagen , wild type , binding domain , microbiology and biotechnology , biology , biochemistry , signal transduction , receptor , gene , g protein , endocrinology
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.