The Collagen-binding A-domains of Integrins α1β1 and α2β1Recognize the Same Specific Amino Acid Sequence, GFOGER, in Native (Triple-helical) Collagens*

By G. Knight, L. Morton, A. R. Peachey, D. Tuckwell, R. Farndale, Michael J. Barnes‡§i. Journal of Biological Chemistry, 2000

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We have previously assigned an integrin α2β1-recognition site in collagen I to the sequence, GFOGERGVEGPOGPA (O = Hyp), corresponding to residues 502–516 of the α1(I) chain and located in the fragment α1(I)CB3 (Knight, C. G., Morton, L. F., Onley, D. J., Peachey, A. R., Messent, 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. This sequence, when in triple-helical conformation, readily supports α2β1-dependent cell adhesion and exhibits divalent cation-dependent binding of isolated α2β1 and recombinant α2A-domain, being at least as active as the parent collagen. Replacement of E by D causes loss of recognition. The same sequence binds integrin α1 A-domain and supports integrin α1β1-mediated cell adhesion. Triple-helical GFOGER completely inhibits α2 A-domain binding to collagens I and IV and α2β1-dependent adhesion of platelets and HT 1080 cells to these collagens. It also fully inhibits α1 A-domain binding to collagen I and strongly inhibits α1β1-mediated adhesion of Rugli cells to this collagen but has little effect on either α1 A-domain binding or adhesion of Rugli cells to collagen IV. We conclude that the sequence GFOGER represents a high-affinity binding site in collagens I and IV for α2β1 and in collagen I for α1β1. Other high-affinity sites in collagen IV mediate its recognition of α1β1.

Subfields: Cancer Research, Hematology, Immunology and Allergy

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In Immunology and Allergy

Citations in the corpus

Collagen self-assembly and the development of tendon mechanical properties. (2003, background): “…matrix collagen fibers via integrin subunits a1b1 and a1b2 (Xu et al., 2000) through a six-residue sequence (glycine– phenylalanine–hydroxyproline–glycine–glutamic acid– arginine) sequence (Knight et al., 2000) that is present in the b2 band of the collagen positive staining band (Fig.”
Enzymatically catalyzed disulfide exchange is required for platelet adhesion to collagen via integrin α2β1 (2003, methodology): “GFOGER, the control peptide GFOGDR which does not recognize α2β1 (38) and the control peptide GPP10 which does not recognize GPVI (42) were used.”
Revealing Early Steps of α2β1 Integrin-mediated Adhesion to Collagen Type I by Using Single-Cell Force Spectroscopy (2007, background): “There are several high-affinity bindings sites for 2 1 on fibrillar collagen type I (Knight et al., 2000; Xu et al., 2000).”
Mammalian collagen IV (2008, background): “It has been shown that a short sequence of GFOGER peptide (O being hydroxyproline) represents a binding site for the α2β1 integrin (Knight et al., 2000).”