Identification of the Regulatory Elements of the Human von Willebrand Factor for Binding to Platelet GPIb

Purified A2 domain of von Willebrand factor binds to the active conformation of von Willebrand factor and blocks the interaction with platelet glycoprotein Ibα

“…Therefore, a potential association between the A1 and A2 domains may be disrupted by shear stress, immobilization, or a modulator such as ristocetin, simultaneously changing the structural conformation of the two domains, and thus leading to the binding to platelet GPIbα and/or the susceptibility to cleavage by ADAMTS‐13. This hypothesis deserves further experimentation using full‐length VWF, because the N‐terminal region of the A1 domain also modulates the interaction between VWF and GPIbα [24,28].…”

Biochemical studies on blood coagulation mechanism

“…Glycosylation is such a candidate modification, since it was previously shown to modulate the levels of expression and degradation of vWF but most importantly to regulate the interaction of vWF A1-loop and its flanking regions with platelet GPIb receptor (317,318).…”

“…Mature vWF is glycosylated, bearing twelve N-linked carbohydrates and ten O-linked carbohydrates. Eight of the 10 O-linked glycans are located within or near the noncontiguous A1-loop flanking region and may have a significant regulatory impact on the interaction with GPIb (318,319). Indeed, two of these O-glycans, at threonine residues 485 and 705, are located within the two peptides found to be the most efficient in inhibition of binding.…”