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 extracellular or intracellular stimuli, suggesting that structural elements within their exo- and cytoplasmic domains cooperate during transmembrane signaling. In this report, we identify a beta turn in the cytoplasmic tail of the alpha v subunit that impacts the ligand binding and conformation of the alpha v beta 3 heterodimer. Cells expressing a mutant alpha v beta 3 heterodimer composed of a truncated alpha v subunit, alpha v1000, lacking 18 carboxyl-terminal amino acids exhibits wild-type receptor structure and function. However, a truncation mutant, alpha v995, 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 changes 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 proteolytic fragment from its ectodomain. These findings demonstrate that the 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 within other alpha subunit cytoplasmic tails suggests that this structural motif may play a role in regulating integrin-mediated bidirectional transmembrane signals.