A beta 3 integrin mutation abolishes ligand binding and alters divalent cation-dependent conformation

Science. 1990 Aug 24;249(4971):915-8. doi: 10.1126/science.2392682.

Abstract

The ligand-binding function of integrin adhesion receptors depends on divalent cations. A mutant alpha IIb beta 3 integrin (platelet gpIIb/IIIa) that lacks ligand recognition shows immunologic evidence of a perturbed interaction with divalent cations. This was found to be caused by a G----T mutation that resulted in an Asp119----Tyr119 substitution in the beta 3 subunit. This residue is proximal to bound ligand and is in a conserved region among integrins that are enriched in oxygenated residues. The spacing of these residues aligns with the calcium-binding residues in EF hand proteins, suggesting interaction with receptor-bound divalent cation as a mechanism of ligand binding common to all integrins.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Aspartic Acid
  • Base Sequence
  • Binding Sites
  • Cell Line
  • Integrins / genetics*
  • Integrins / metabolism
  • Ligands
  • Macromolecular Substances
  • Molecular Sequence Data
  • Mutation*
  • Oligonucleotide Probes
  • Platelet Membrane Glycoproteins / genetics*
  • Platelet Membrane Glycoproteins / metabolism
  • Polymerase Chain Reaction
  • Protein Conformation
  • Sequence Homology, Nucleic Acid
  • Tyrosine

Substances

  • Integrins
  • Ligands
  • Macromolecular Substances
  • Oligonucleotide Probes
  • Platelet Membrane Glycoproteins
  • Aspartic Acid
  • Tyrosine