title: A beta turn in the cytoplasmic tail of the integrin alpha v subunit influences conformation and ligand binding of alpha v beta 3.
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 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.
authors.affiliation: Scripps Research Institute, Department of Immunology, La Jolla, California 92037.
authors.forename: E J
authors.initials: EJ
authors.lastname: Filardo
authors.forename: D A
authors.initials: DA
authors.lastname: Cheresh
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002448:Cell Adhesion; D002918:Chymotrypsin / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism; D003593:Cytoplasm / Q000648:ultrastructure; D004252:DNA Mutational Analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005340:Fibrinogen / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D016023:Integrins / Q000737:chemistry / Q000648:ultrastructure*; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D009842:Oligopeptides / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D016024:Receptors, Cytoadhesin / Q000737:chemistry / Q000648:ultrastructure*; D019030:Receptors, Vitronectin; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D019096:Vitronectin
chemical_list: D006023:Glycoproteins; D016023:Integrins; D008024:Ligands; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; D016024:Receptors, Cytoadhesin; D019030:Receptors, Vitronectin; D019096:Vitronectin; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen; D003094:Collagen; D002918:Chymotrypsin