Integrins are a family of α/β heterodimers of cell adhesion receptors that mediate cell-extracellular matrix and cell-cell interactions. Both α and β subunits have a large extracellular domain and a short cytoplasmic domain. The α subunit has seven sequence repeats of 60-70 residues in its N-terminal region. The β-propeller model, in which seven four-stranded β-sheets are arranged in a torus around a pseudosymmetry axis, has been proposed as a structural model of these seven repeats. Several predicted loops critical for ligand binding have been identified in the upper face of the proposed β-propeller model. Several α subunits (e.g., α2, αL and αM) have I-domains of about 200 residues inserted between their second and third repeats. These I-domains adopt a Rossman-fold structure and have major ligand and cation binding sites (the MIDAS site) on their surfaces. The β subunit has an I-domain-like structure in its N-terminal region. This structure includes multiple sequences/conserved oxygenated residues critical for ligand binding, and non-conserved residues critical for ligand specificities. Several 'activation-dependent' epitopes have been identified in the Cys-rich (stalk) region of β1. It has yet to be determined how these multiple ligand binding sites in the α and β subunits are involved in ligand binding, and how conformational changes on activation/ligand occupancy relate to signal transduction.
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