LIGAND AND CATION-BINDING ARE DUAL FUNCTIONS OF A DISCRETE SEGMENT OF THE INTEGRIN BETA(3) SUBUNIT - CATION DISPLACEMENT IS INVOLVED IN LIGAND-BINDING

The alpha(IIb)beta(3) integrin binds Arg-Gly-Asp-containing (RGD-containing) ligands in a cation-dependent interaction. A fourteen amino acid sequence, beta(3)(118-131), and an antibody to it, inhibited ligand binding functions of alpha(IIb)beta s, and a 1:1 stoichiometric beta(3)(118-131)-RGD complex was detected by mass spectroscopy. Cation binding to Ps(118-131) was demonstrated by terbium luminescence and mass spectroscopy. Notably, ligand displaced cation from the beta(3)(118-131) peptide and also from purified alpha(IIb)beta(3). Thus, beta(3)(118-131), a highly conserved region in integrin beta subunits, binds both ligand and cation. Formation of a ternary complex between cation, ligand, and receptor, with subsequent displacement of cation from beta(3)(118-131)and a second site within the receptor, may be central to the mechanism of ligand recognition by integrins.