A BETA-TURN IN THE CYTOPLASMIC TAIL OF THE INTEGRIN ALPHA-V SUBUNIT INFLUENCES CONFORMATION AND LIGAND-BINDING OF ALPHA-V-BETA-3

Integrins undergo conformational alterations in response to extracellu lar or intracellular stimuli, suggesting that structural elements with in their exo- and cytoplasmic domains cooperate during transmembrane s ignaling. In this report, we identify a beta turn in the cytoplasmic t ail of the alpha v subunit that impacts the ligand binding and conform ation of the alpha v beta 3 heterodimer. Cells expressing a mutant alp ha v beta 3 heterodimer composed of a truncated alpha v subunit, alpha v1000, lacking 18 carboxyl-terminal amino acids exhibits wild-type re ceptor structure and function. However, a truncation mutant, alpha v99 5, lacking five additional residues (PPQEE), which define a beta turn, is deficient in vitronectin and fibrinogen adhesion. This alteration in adhesive function is associated with two detectable structural chan ges in the alpha v beta 3 heterodimer. First, the alpha v995 membrane- spanning light chain exhibits retarded electrophoretic mobility on SDS -polyacrylamide gels. Second, the alpha v995 beta 3 receptor shows an altered chymotryptic profile as measured by the loss of a 39-kDa prote olytic fragment from its ectodomain. These findings demonstrate that t he ligand binding and structural properties of the intact alpha v beta 3 heterodimer can be influenced by a beta turn within the cytoplasmic tail of its alpha v subunit. The presence of homologous beta turns wi thin other alpha subunit cytoplasmic tails suggests that this structur al motif may play a role in regulating integrin-mediated bidirectional transmembrane signals.