<p>Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions, make transmembrane connections to the cytoskeleton and activate many intracellular signalling pathways [<cite idref="PUB00009789"/>, <cite idref="PUB00035000"/>]. The integrin receptors are composed of alpha and beta subunit heterodimers. Each subunit crosses the membrane once, with most of the polypeptide residing in the extracellular space, and has two short cytoplasmic domains. Some members of this family have EGF repeats at the C terminus and also have a vWA domain inserted within the integrin domain at the N terminus.</p><p> Most integrins recognise relatively short peptide motifs, and in general require an acidic amino acid to be present. Ligand specificity depends upon both the alpha and beta subunits [<cite idref="PUB00035002"/>]. There are at least 18 types of alpha and 8 types of beta subunits recognised in humans [<cite idref="PUB00015915"/>]. Each alpha subunit tends to associate only with one type of beta subunit, but there are exceptions to this rule [<cite idref="PUB00015985"/>]. Each association of alpha and beta subunits has its own binding specificity and signalling properties. Many integrins require activation on the cell surface before they can bind ligands. Integrins frequently intercommunicate, and binding at one integrin receptor activate or inhibit another.</p><p> The structure of unliganded alphaV beta3 showed the molecule to be folded, with the head bent over towards the C termini of the legs which would normally be inserted into the membrane [<cite idref="PUB00035001"/>]. The head comprises a beta propeller domain at the end terminus of the alphaV subunit and an I/A domain inserted into a loop on the top of the hybrid domain in the beta subunit. The I/A domain consists of a Rossman fold with a core of beta parallel sheets surrounded by amphipathic alpha helices. </p>Some alpha subunits are cleaved post-translationally to produce a heavy and a light chain linked by a disulphidebond [<cite idref="PUB00000811"/>, <cite idref="PUB00001505"/>]. Integrin alpha chains share a conserved sequence which is found atthe beginning of the cytoplasmic domain, just after the end of thetransmembrane region. Within the N-terminal domain of alpha subunits, seven sequence repeats, eachof approximately 60 amino acids, have been found [<cite idref="PUB00006166"/>]. It has been predicted that these repeats assume the beta-propeller fold. The domains contain seven four-stranded beta-sheets arranged in a torus around a pseudosymmetry axis[<cite idref="PUB00005772"/>]. Integrin ligands and a putative Mg²⁺ ion are predicted to bind to theupper face of the propeller, in a manner analogous to the way in which thetrimeric G-protein beta subunit (G beta) (which also has a beta-propellerfold) binds the G protein alpha subunit [<cite idref="PUB00005772"/>].<p>Integrin cytoplasmic domains are normally less than 50 amino acids in length, with the beta-subunit sequences exhibiting greater homology to each other than the alpha-subunit sequences [<cite idref="PUB00011882"/>]. This is consistent with current evidence that the beta subunit is the principal site for binding of cytoskeletal and signalling molecules, whereas the alpha subunit has a regulatory role. The first ten residues of the alpha-subunit cytoplasmic domain appear to form an alpha helix that is terminated by a proline residue. The remainder of the domain is highly acidic in nature and this loops back to contact the membrane-proximal lysine anchor residue.</p> Integrin alpha chain