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A beta turn in the cytoplasmic tail of the integrin alpha v subunit influences conformation and ligand binding of alpha v beta 3
Journal article   Open access   Peer reviewed

A beta turn in the cytoplasmic tail of the integrin alpha v subunit influences conformation and ligand binding of alpha v beta 3

E J Filardo and D A Cheresh
The Journal of biological chemistry, Vol.269(6), pp.4641-4647
02/11/1994
DOI: 10.1016/S0021-9258(17)41824-2
PMID: 7508446
url
https://doi.org/10.1016/S0021-9258(17)41824-2View
Published (Version of record) Open Access

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.
 Molecular Weight Humans Glycoproteins - metabolism Integrins - chemistry Oligodeoxyribonucleotides - chemistry Molecular Sequence Data Vitronectin Cytoplasm - ultrastructure Structure-Activity Relationship Receptors, Cytoadhesin - ultrastructure DNA Mutational Analysis Base Sequence Tumor Cells, Cultured Amino Acid Sequence Protein Structure, Secondary Electrophoresis, Polyacrylamide Gel Oligopeptides - metabolism Cell Adhesion Integrins - ultrastructure Chymotrypsin - pharmacology Collagen - metabolism Membrane Proteins - chemistry Receptors, Cytoadhesin - chemistry Fibrinogen - metabolism Protein Binding Ligands Protein Conformation Receptors, Vitronectin In Vitro Techniques

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