title: Distinct structural requirements for interaction of the integrins alpha 5 beta 1, alpha v beta 5, and alpha v beta 6 with the central cell binding domain in fibronectin.
abstract: At least 10 different members of the integrin family have been reported to bind to fibronectin, and eight of these interact with the arginine-glycine-aspartic acid (RGD) site in the tenth type III repeat. However, studies utilizing recombinant fibronectin fragments have shown that for three of these, alpha 5 beta 1, alpha IIb beta 3, and alpha v beta 3, the structural requirements for binding to fibronectin differ. In the present study, we report that two additional integrins, alpha v beta 6, and alpha v beta 5 also demonstrate unique requirements for interaction with recombinant fibronectin fragments, alpha v beta 6, like alpha v beta 3, can support cell adhesion to the RGD-containing tenth repeat alone, and does not require the presence of a synergy site in the adjacent ninth repeat. In the cells used in this study, alpha v beta 5 only minimally supported adhesion to intact fibronectin, but did support adhesion to fragments composed of the eighth, ninth and tenth repeats or the tenth repeat, alone. Mutant fragments in which the eighth and tenth repeats were adjacent to one another enhanced adhesion mediated by alpha v beta 5, as well as adhesion mediated by alpha v beta 6. alpha v beta 5 and alpha v beta 6-mediated adhesion to all fibronectin fragments required interaction with the RGD site, as inferred by inhibition of adhesion with an RGD-containing peptide. These data suggest that each integrin that interacts with the RGD site in fibronectin has unique structural requirements for this interaction.
authors.affiliation: Department of Medicine, University of California, San Francisco 94143, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: T
authors.initials: T
authors.lastname: Maeda
authors.forename: K
authors.initials: K
authors.lastname: Sekiguchi
authors.forename: D
authors.initials: D
authors.lastname: Sheppard
mesh_terms: D000951:Antigens, Neoplasm; D001665:Binding Sites; D002448:Cell Adhesion / Q000502:physiology; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D015321:Gene Rearrangement; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017469:Receptors, Fibronectin / Q000378:metabolism*; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D017384:Sequence Deletion; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D005353:Fibronectins; D016023:Integrins; D009842:Oligopeptides; D010446:Peptide Fragments; D017469:Receptors, Fibronectin; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins; C064660:integrin alphaVbeta5; C073878:integrin alphavbeta6; C047981:arginyl-glycyl-aspartic acid