title: The A-domain of integrin alpha 2 binds specifically to a range of collagens but is not a general receptor for the collagenous motif.
abstract: Integrin alpha 2 beta 1 is a major cellular receptor for collagens, but the molecular basis of its function is unknown. The alpha 2 subunit contains a von Willebrand factor A-domain (I-domain) in its N-terminal region, and it has been demonstrated recently that this domain binds specifically to collagen I. This interaction requires divalent cations (e.g., Mg2+) and native collagen conformation, as does binding of the parent integrin to collagen. The alpha 2 A-domain therefore has a number of functional similarities to the parent integrin, alpha 2 beta 1. However, while sequence specificity has been demonstrated for the parent integrin, no such observations have been made for the A-domain. In particular, it is not known whether the A-domain is responsible for sequence-specific recognition of collagens or whether it binds to the genetic collagenous motif. To investigate the ligand specificity of the alpha 2 A-domain, its binding to a range of collagenous ligands has been studied, with cation dependence, collagen triple-helicity, and inhibition by function-blocking antibodies as criteria for specificity. Binding of the parent integrin was examined for comparison. The alpha 2 A-domain was found to bind specifically to collagens I, II, IV and XI. The complement component C1q has a collagenous domain but this was unable to support specific binding of alpha 2 A-domain or alpha 2 beta 1. Furthermore, synthetic triple-helical collagenous peptides failed to act as specific ligands. In conclusion, the alpha 2 A-domain binds specifically to a range of extracellular matrix collagens, but it is not a receptor for all collagenous triple helices. By inference, these findings indicate the existence of an integrin-specific sequence motif within collagenous ligands recognised by the alpha 2 A-domain.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, UK. tuckwell@fs2.scg.man.ac.uk
authors.forename: D S
authors.initials: DS
authors.lastname: Tuckwell
authors.forename: K B
authors.initials: KB
authors.lastname: Reid
authors.forename: M J
authors.initials: MJ
authors.lastname: Barnes
authors.forename: M J
authors.initials: MJ
authors.lastname: Humphries
mesh_terms: D015703:Antigens, CD / Q000737:chemistry / Q000378:metabolism*; D003094:Collagen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015922:Complement C1q / Q000378:metabolism; D039421:Integrin alpha2; D016023:Integrins / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D038981:Receptors, Collagen; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014841:von Willebrand Factor / Q000737:chemistry
chemical_list: D015703:Antigens, CD; D039421:Integrin alpha2; D016023:Integrins; D009842:Oligopeptides; D010446:Peptide Fragments; D038981:Receptors, Collagen; D011994:Recombinant Proteins; D014841:von Willebrand Factor; D015922:Complement C1q; D003094:Collagen