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PubMed · 2392682

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

J C Loftus·T E O'Toole·E F Plow·A Glass·A L Frelinger·M H Ginsberg
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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.

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Amino Acid SequenceAnimalsAspartic AcidBase SequenceBinding SitesCell LineIntegrinsLigandsMacromolecular SubstancesMolecular Sequence DataMutationOligonucleotide ProbesPlatelet Membrane GlycoproteinsPolymerase Chain ReactionProtein ConformationSequence Homology, Nucleic AcidTyrosineComparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.

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J C Loftus, T E O'Toole, E F Plow, A Glass, A L Frelinger, M H Ginsberg. 1990-08-24. A beta 3 integrin mutation abolishes ligand binding and alters divalent cation-dependent conformation.. https://doi.org/10.1126/science.2392682

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