Effects of conformational activation of integrin α1I and α2I domains on selective recognition of laminin and collagen subtypes

Collagen receptor integrins α1β1 and α2β1 can selectively recognize different collagen subtypes. Here we show that their αI domains can discriminate between laminin isoforms as well: α1I and α2I recognized laminin-111, -211 and -511, whereas their binding to laminin-411 was negligible. Residue Arg-218 in α1 was found to be instrumental in high-avidity binding. The gain-of-function mutation E318W makes the α2I domain to adopt the “open” high-affinity conformation, while the wild-type α2I domain favors the “closed” low-affinity conformation. The E318W mutation markedly increased α2I domain binding to the laminins (-111, -211 and -511), leading us to propose that the activation state of the α2β1 integrin defines its role as a laminin receptor. However, neither wild-type nor α2IE318W domain could bind to laminin-411. α2IE318W also bound tighter to all collagens than α2I wild-type, but it showed reduced ability to discriminate between collagens I, IV and IX. The corresponding mutation, E317A, in the α1I domain transformed the domain into a high-avidity binder of collagens I and IV. Thus, our results indicate that conformational activation of integrin α1I and α2I domains leads to high-avidity binding to otherwise disfavoured collagen subtypes.