The ligand-binding function of integrin adhesion receptors depends on divalent cations. A mutant α_IIbβ₃ 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 β₃ 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.