aIIbb3 and Its Antagonism at the New Millennium
Edward F. Plow (1) , Czeslaw S. Cierniewski (2) , Zihui Xiao (1) , Thomas A. Haas (1) , Tatiana V. Byzova (1)
(1) Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Department of Molecular Cardiology, Cleveland Clinic Foundation, Cleveland, OH, USA, (2) Department of Biophysics, Medical University in Lodz, Lodz, Poland
Summary Because of its major role in regulating platelet functions and itsprominence on the cell surface, integrin aIIbb3 has been the subject ofintensive investigations. Such studies have provided substantial insightsinto its structure-function relationships and have led to the developmentof anti-thrombotic drugs that target the receptor. Nevertheless,recent findings have indicated that our understanding of the structureand function of aIIbb3 remains inadequate. This article addresses twoaspects of still evolving aIIbb3 function: 1) the interface between aIIbb3and the blood coagulation system, resulting from interaction of prothrombinwith the receptor; and 2) the molecular basis for recognitionof the RGD and the fibrinogen g-chain peptide ligands by aIIbb3. Asillustrated by these two examples, there is still much to be learnedabout aIIbb3 if we are to fully appreciate its functions and its potentialas a therapeutic target.