A β3 integrin mutation abolishes ligand binding and alters divalent cation-dependent conformation

Joseph C. Loftus, Timothy E. O'Toole, Edward F. Plow, Alison Glass, Andrew L. Frelinger, Mark H. Ginsberg

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Abstract

The ligand-binding function of integrin adhesion receptors depends on divalent cations. A mutant αIIbβ3 integrin (platelet gpIIb/IIIa) that lacks ligand recognition shows immunologic evidence ofa 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 ofthese 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.

Original languageEnglish (US)
Pages (from-to)915-918
Number of pages4
JournalScience
Volume249
Issue number4971
DOIs
StatePublished - 1990

ASJC Scopus subject areas

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    Loftus, J. C., O'Toole, T. E., Plow, E. F., Glass, A., Frelinger, A. L., & Ginsberg, M. H. (1990). A β3 integrin mutation abolishes ligand binding and alters divalent cation-dependent conformation. Science, 249(4971), 915-918. https://doi.org/10.1126/science.2392682