Crystal structure of the α1β1 integrin I‐domain: insights into integrin I‐domain function

Abstract

The α1β1 integrin is a major cell surface receptor for collagen. Ligand binding is mediated, in part, through a ∼200 amino acid inserted ‘I’‐domain contained in the extracellular part of the integrin α chain. Integrin I‐domains contain a divalent cation binding (MIDAS) site and require cations to interact with integrin ligands. We have determined the crystal structure of recombinant I‐domain from the rat α1β1 integrin at 2.2 Å resolution in the absence of divalent cations. The α1 I‐domain adopts the dinucleotide binding fold that is characteristic of all I‐domain structures that have been solved to date and has a structure very similar to that of the closely related α2β1 I‐domain which also mediates collagen binding. A unique feature of the α1 I‐domain crystal structure is that the MIDAS site is occupied by an arginine side chain from another I‐domain molecule in the crystal, in place of a metal ion. This interaction supports a proposed model for ligand‐induced displacement of metal ions. Circular dichroism spectra determined in the presence of Ca²⁺, Mg²⁺ and Mn²⁺ indicate that no changes in the structure of the I‐domain occur upon metal ion binding in solution. Metal ion binding induces small changes in UV absorption spectra, indicating a change in the polarity of the MIDAS site environment.