THE A-DOMAIN OF INTEGRIN ALPHA-2 BINDS SPECIFICALLY TO A RANGE OF COLLAGENS BUT IS NOT A GENERAL RECEPTOR FOR THE COLLAGENOUS MOTIF

Integrin alpha 2 beta 1 is a major cellular receptor for collagens, bu t 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 num ber of functional similarities to the parent integrin. alpha 2 beta 1. However, while sequence specificity has been demonstrated for the par ent integrin, no such observations have bean made for the A-domain. In particular, it is not known whether the A-domain is responsible for s equence-specific recognition of collagens or whether it binds to the g eneric collagenous motif. To investigate the ligand specificity of the alpha 2 A-domain, its binding to a range of collagenous ligands has b een studied, with cation dependence, collagen triple-helicity, and inh ibition by function-blocking antibodies as criteria for specificity. B inding 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 u nable to support specific binding of alpha 2 A-domain or alpha 2 beta 1. Furthermore, synthetic triple-helical collagenous peptides failed t o act as specific ligands. In conclusion, the alpha 2 A-domain binds s pecifically to a range of extracellular matrix collagens, but it is no t a receptor for all collagenous triple helices. By inference, these f indings indicate the existence of an integrin-specific sequence motif within collagenous ligands recognised by the alpha 2 A-domain.