HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Requirement of leucine-rich repeats of glycoprotein (GP) Iba for shear-dependent and static binding of von Willebrand factor to the platelet membrane GP Ib–IX-V complex
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چکیده
The platelet glycoprotein (GP) Ib–IX-V complex mediates adhesion to von Willebrand factor (vWf) in (patho)physiologic thrombus formation. The vWf-binding site on GP Ib–IX-V is within the N-terminal 282 residues of GP Iba, which consist of an N-terminal flanking sequence (His-1– Ile-35), 7 leucine-rich repeats (Leu-36–Ala200), a C-terminal flank (Phe-201–Gly268), and a sulfated tyrosine sequence (Asp-269–Glu-282). We have used mammalian cell expression of canine–human chimeras of GP Iba, corresponding to precise structural boundaries, to demonstrate the first specific requirement for individual leucine-rich repeats for binding of vWf either induced by a modulator, ristocetin, or under hydrodynamic flow. Implicit in this approach was that the GP Iba chimeras retained a functional conformation, a supposition confirmed by analyzing restoration of function to reversed human–canine chimeras and demonstrating that all chimeras bound vWf activated by botrocetin, a modulator that is indiscriminate between species. Leucine-rich repeats 2, 3, and 4 of GP Iba were identified as being critical for vWf adhesion to GP Ib–IX-V. (Blood. 2000;95:903910)
منابع مشابه
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Ristocetin-dependent, but not botrocetin-dependent, binding of von Willebrand factor to the platelet glycoprotein Ib-IX-V complex correlates with shear-dependent interactions
Under conditions of high shear stress, both hemostasis and thrombosis are initiated by the interaction of the platelet membrane glycoprotein (GP) Ib-IX-V complex with its adhesive ligand, von Willebrand factor (vWF), in the subendothelial matrix or plasma. This interaction involves the A1 domain of vWF and the N-terminal extracellular region of GP Iba (His-1-Glu-282), and it can also be induced...
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