Selective Binding of Collagen Subtypes by Integrin alpha sub(1)I, alpha sub(2)I, and alpha sub(10)I Domains

• Published in: The Journal of biological chemistry Vol. 276; no. 51; pp. 48206 - 48212
• Main Authors: Tulla, M, Pentikaeinen, O T, Viitasalo, T, Kaepylae, J, Impola, U, Nykvist, P, Nissinen, L, Johnson, MS, Heino, J
• Format: Journal Article
• Language: English
• Published: 21.12.2001
• Subjects: Integrin^a10^b1; Integrin^a11^b1; Integrin^a1^b1; Integrin^a2^b1
• ISSN: 0021-9258

Four integrins, namely alpha sub(1) beta sub(1), alpha sub(2) beta sub(1), alpha sub(10) beta sub(1), and alpha sub(11) beta sub(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 alpha subunit. We have produced the human integrin alpha sub(10)I domain as a recombinant protein to reveal its ligand binding specificity. In general, alpha sub(10)I did recognize collagen types I-VI and laminin-1 in a Mg super(2+)-dependent manner, whereas its binding to tenascin was only slightly better than to albumin. When alpha sub(10)I was tested together with the alpha sub(1)I and alpha sub(2)I domains, all three I domains seemed to have their own collagen binding preferences. The integrin alpha sub(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 alpha sub(1)I had the opposite binding pattern. The integrin alpha sub(10)I domain was similar to the alpha sub(1)I domain in that it bound very well to collagen types IV and VI. Based on the previously published atomic structures of the alpha sub(1)I and alpha sub(2)I domains, we modeled the structure of the alpha sub(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 alpha I domains, and their binding to types I, IV, and VI collagen was tested. In the alpha sub(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 alpha sub(1)I and alpha sub(10)I domains is oppositely charged (Arg-218). The mutation D219R in the alpha sub(2)I domain changed the ligand binding pattern to resemble that of the alpha sub(1)I and alpha sub(10)I domains and, vice versa, the R218D mutation in the alpha sub(1)I and alpha sub(10)I domains created an alpha sub(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.