Shielding of the A1 Domain by the D′D3 Domains of von Willebrand Factor Modulates Its Interaction with Platelet Glycoprotein Ib-IX-V *

摘要: Soluble von Willebrand factor (VWF) has a low affinity for platelet glycoprotein (GP) Ibα and needs immobilization and/or high shear stress to enable binding of its A1 domain the receptor. The previously described anti-VWF monoclonal antibody 1C1E7 enhances VWF/GPIbα recognizes an epitope in amino acids 764–1035 region N-terminal D′D3 domains. In this study we demonstrated that negatively modulates VWF/GPIb-IX-V interaction; (i) deletion VWF augmented GPIbα, suggesting inhibitory role region, (ii) isolated inhibited GPIbα interaction mutant lacking indicating intramolecular interactions limit accessibility domain, (iii) using panel antibodies, next showed is close proximity with soluble but not when was immobilized; (iv) destroying resulted increased GPIbα. Our results support model translocation allows suggested shielding by then becomes disrupted immobilization.