The A-Domain of Integrin α2 Binds Specifically to a Range of Collagens but is not a General Receptor for the Collagenous Motif


D. S. Tuckwell, Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, Stopford Building, Oxford Road, Manchester, M13 9PT, UK
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Integrin α2β1 is a major cellular receptor for collagens, but the molecular basis of its function is unknown. The α2 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 α2 A-domain therefore has a number of functional similarities to the parent integrin, α2β1. 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 generic collagenous motif. To investigate the ligand specificity of the α2 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 α2 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 α2 A-domain or α2β1. Furthermore, synthetic triple-helical collagenous peptides failed to act as specific ligands. In conclusion, the α2 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 α2 A-domain.