Crystal structure of the alpha 1 beta 1 integrin I-domain: insights into integrin I-domain function

The alpha 1 beta 1 integrin is a major cell surface receptor for collagen. Ligand binding is mediated, in part, through a similar to 200 amino acid in serted 'I'-domain contained in the extracellular part of the integrin a cha in. Integrin I-domains contain a divalent cation binding (MIDAS) site and r equire cations to interact with integrin ligands, We have determined the cr ystal structure of recombinant I-domain from the rat alpha 1 beta 1 integri n at 2.2 Angstrom resolution in the absence of divalent cations, The al I-d omain adopts the dinucleotide binding fold that is characteristic of all I- domain structures that have been solved to date and has a structure very si milar to that of the closely related alpha 2 beta 1 I-domain which also med iates collagen binding. A unique feature of the alpha 1 I-domain crystal st ructure is that the MIDAS site is occupied by an arginine side chain from a nother I-domain molecule in the crystal, in place of a metal ion, This inte raction supports a proposed model for ligand-induced displacement of metal ions. Circular dichroism spectra determined in the presence of Ca2+, Mg2+ a nd Mn2+ indicate that no changes in the structure of the I-domain occur upo n metal ion binding in solution. Metal ion binding induces small changes in UV absorption spectra, indicating a change in the polarity of the MIDAS si te environment. (C) 1999 Federation of European Biochemical Societies.