The collagen-binding A-domains of integrins alpha(1)beta(1) and alpha(2)beta(1) recognize the same specific amino acid sequence, GFOGER, in native (triple-helical) collagens

We have previously assigned an integrin alpha(2)beta(1)-recognition site in collagen I to the sequence, GFOGERGVEG-POGPA (O = Hyp), corresponding to r esidues 502-516 of the alpha(1)(I) chain and located in the fragment alpha( I)(I)CB3 (Knight, C. G., Morton, L. F., Onley, D. J., Peachey, A. R., Messe nt, A. J., Smethurst, P. A., Tuckwell, D. S., Farndale, R. W., and Barnes, M. J. (1998) J. Biol. Chem. 273, 33287-33294). In this study, we show that recognition is entirely contained within the six-residue sequence GFOGER. T his sequence, when in triple-helical conformation, readily supports alpha(2 )beta(1)-dependent cell adhesion and exhibits divalent cation-dependent bin ding of isolated alpha(2)beta(1) and recombinant alpha(2) A-domain, being a t least as active as the parent collagen. Replacement of E by D causes loss of recognition. The same sequence binds integrin alpha(2) A-domain and sup ports integrin alpha(1)beta(1)-mediated cell adhesion. Triple-helical GFOGE R completely inhibits alpha(2) A-domain binding to collagens I and IV and a lpha(2)beta(1)-dependent adhesion of platelets and HT 1080 cells to these c ollagens. It also fully inhibits alpha(1) A-domain binding to collagen I an d strongly inhibits alpha(1)beta(1)-mediated adhesion of Rugli cells to thi s collagen but has little effect on either alpha 1 A-domain binding or adhe sion of Rugli cells to collagen IV. We conclude that the sequence GFOGER re presents a high-affinity binding site in collagens I and IV for alpha(2)bet a(1) and in collagen I for alpha(1)beta(1). Other high-affinity sites in co llagen IV mediate its recognition of alpha(1)beta(1).