A β turn in the cytoplasmic tail of the integrin αv subunit influences conformation and ligand binding of αvβ3

Abstract

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 β turn in the cytoplasmic tail of the αv subunit that impacts the ligand binding and conformation of the αvβ3 heterodimer. Cells expressing a mutant αvβ3 heterodimer composed of a truncated αv subunit, αv1000, lacking 18 carboxyl-terminal amino acids exhibits wild- type receptor structure and function. However, a truncation mutant, αv995, lacking five additional residues (PPQEE), which define a β turn, is deficient in vitronectin and fibrinogen adhesion. This alteration in adhesive function is associated with two detectable structural changes in the αvβ3 heterodimer. First, the αv995 membrane-spanning light chain exhibits retarded electrophoretic mobility on SDS-polyacrylamide gels. Second, the αv995β3 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 αvβ3 heterodimer can be influenced by a β turn within the cytoplasmic tail of its αv subunit. The presence of homologous β turns within other α subunit cytoplasmic tails suggests that this structural motif may play a role in regulating integrin-mediated bidirectional transmembrane signals.