Selective Binding of Collagen Subtypes by Integrin α1I, α2I, and α10I Domains

Four integrins, namely α 1 β 1 , α 2 β 1 , α 10 β 1 , and α 11 β 1 , form a special subclass of cell adhesion receptors. They are all collagen receptors, and they recognize their ligands with an inserted domain (I domain) in their α subunit. We have produced the human integrin α 10 I domain as a recombinant protein to reveal its ligand binding specificity. In general, α 10 I did recognize collagen types I–VI and laminin-1 in a Mg 2+ -dependent manner, whereas its binding to tenascin was only slightly better than to albumin. When α 10 I was tested together with the α 1 I and α 2 I domains, all three I domains seemed to have their own collagen binding preferences. The integrin α 2 I domain bound much better to fibrillar collagens (I–III) than to basement membrane type IV collagen or to beaded filament-forming type VI collagen. Integrin α 1 I had the opposite binding pattern. The integrin α 10 I domain was similar to the α 1 I domain in that it bound very well to collagen types IV and VI. Based on the previously published atomic structures of the α 1 I and α 2 I domains, we modeled the structure of the α 10 I domain. The comparison of the three I domains revealed similarities and differences that could potentially explain their functional differences. Mutations were introduced into the αI domains, and their binding to types I, IV, and VI collagen was tested. In the α 2 I domain, Asp-219 is one of the amino acids previously suggested to interact directly with type I collagen. The corresponding amino acid in both the α 1 I and α 10 I domains is oppositely charged (Arg-218). The mutation D219R in the α 2 I domain changed the ligand binding pattern to resemble that of the α 1 I and α 10 I domains and, vice versa, the R218D mutation in the α 1 I and α 10 I domains created an α 2 I domain-like ligand binding pattern. Thus, all three collagen receptors appear to differ in their ability to recognize distinct collagen subtypes. The relatively small structural differences on their collagen binding surfaces may explain the functional specifics.