α11β1 integrin recognizes the GFOGER sequence in interstitial collagens

Abstract

The integrins α1β1, α2β1, α10β1 and α11β1 are referred to as a collagen receptor subgroup of the integrin family. Recently, both α1β1 and α2β1 integrins have been shown to recognize triple-helical GFOGER (where single letter amino acid nomenclature is used, O = hydroxyproline) or GFOGER-like motifs found in collagens, despite their distinct binding specificity for various collagen subtypes. In the present study we have investigated the mechanism whereby the latest member in the integrin family, α11β1, recognizes collagens using C2C12 cells transfected with α11 cDNA and the bacterially expressed recombinant α11 I domain. The ligand binding properties of α11β1 were compared with those of α2β1. Mg2+-dependent α11β1 binding to type I collagen required micromolar Ca2+ but was inhibited by 1 mM Ca2+, whereas α2β1-mediated binding was refractory to millimolar concentrations of Ca2+. The bacterially expressed recombinant α11 I domain preference for fibrillar collagens over collagens IV and VI was the same as the α2 I domain. Despite the difference in Ca2+ sensitivity, α11β1-expressing cells and the α11 I domain bound to helical GFOGER sequences in a manner similar to α2β1-expressing cells and the α2 I domain. Modeling of the α I domain-collagen peptide complexes could partially explain the observed preference of different I domains for certain GFOGER sequence variations. In summary, our data indicate that the GFOGER sequence in fibrillar collagens is a common recognition motif used by α1β1, α2β1, and also α11β1 integrins. Although α10 and α11 chains show the highest sequence identity, α2 and α11 are more similar with regard to collagen specificity. Future studies will reveal whether α2β1 and α11β1 integrins also show overlapping biological functions.