The αIIb and αv integrins have been shown to play a significant role in a variety of disease processes. αIIbβ3 is a platelet-specific fibrinogen receptor that is critical for thrombosis and hemostasis. Determination of the basis of ligand recognition by αIIbβ3 is essential for modulation of platelet function. To identify αIIb residues involved in αIIbβ3 ligand binding function, cells expressing a constitutively active variant of αIIbβ3 were randomly mutagenized and selected for loss of αIIbβ3 ligand binding function. One mutant isolated in this manner contained a single amino acid substitution at position 96 in αIIb (Ser96→Leu). Cells expressing this αIIb mutant did not bind the ligand mimetic antibody PACI or adhere to fibrinogen. In addition, the mutant receptor did not bind to an RGD affinity matrix. Substitution of conserved serine residues at position I in β strand A of all seven repeats of αIIb similarly inhibited ligand binding to αIIbβ3. αIIbS96 maps to the central cavity of the β-propeller fold of the αIIb subunit immediately adjacent to a structurally important sequence at the center of the α and β subunit interface. In contrast, substitution of the analogous residues in αv or α4 did not disrupt the ligand binding function of αvβ3 or α4β1. These data support a potential unique structural or mechanistic role for this residue in αIIbβ3 receptor function.
|Original language||English (US)|
|Number of pages||10|
|Journal||Thrombosis and Haemostasis|
|State||Published - Nov 2003|
- Flow cytometry
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