title: Structural basis of integrin-mediated signal transduction.
abstract: Integrins are a family of alpha/beta heterodimers of cell adhesion receptors that mediate cell-extracellular matrix and cell-cell interactions. Both alpha and beta subunits have a large extracellular domain and a short cytoplasmic domain. The alpha subunit has seven sequence repeats of 60-70 residues in its N-terminal region. The beta-propeller model, in which seven four-stranded beta-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 beta-propeller model. Several alpha subunits (e.g., alpha 2, alpha L and alpha M) 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 beta subunit has an I-domain-like structure in its N-terminal region. This structure includes multiple sequences/conserved oxygenated residues critical for ligand binding (e.g., Asp-119 in beta 3), and non-conserved residues critical for ligand specificities. Several "activation-dependent" epitopes have been identified in the Cys-rich (stalk) region of beta 1. It has yet to be determined how these multiple ligand binding sites in the alpha and beta subunits are involved in ligand binding, and how conformational changes on activation/ligand occupancy relate to signal transduction.
authors.affiliation: Department of Vascular Biology, Scripps Research Institute, La Jolla, California, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Takada
authors.forename: T
authors.initials: T
authors.lastname: Kamata
authors.forename: A
authors.initials: A
authors.lastname: Irie
authors.forename: W
authors.initials: W
authors.lastname: Puzon-McLaughlin
authors.forename: X P
authors.initials: XP
authors.lastname: Zhang
mesh_terms: D000818:Animals; D006801:Humans; D016023:Integrins / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008954:Models, Biological; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: D016023:Integrins; D008024:Ligands