title: Structural determinants within platelet glycoprotein Ibalpha involved in its binding to von Willebrand factor.
abstract: Platelet adhesion to subendothelial structures upon injury to a vessel wall is one of the first steps in a sequence of reactions critical for the formation of a haemostatic plug, or in diseased vessels for the development of an arterial thrombus. This adhesion process is mediated by an interaction between the glycoprotein (GP) Ib-V-IX complex on the platelet surface with von Willebrand Factor (vWF), associated with collagen on the subendothelial surface. After this initial adhesion, platelets will activate, resulting in recruitment of additional platelets and adherence to each other to form the platelet plug or developing thrombus. Several studies to date have attempted to identify the regions of the GPIb-V-IX complex that are critical for binding to vWF. The vWF binding site is contained in the 45 kDa N-terminal domain of the GPIbalpha chain. This N-terminal domain is characterized by a structural motif consisting of 7 leucine-rich repeats (LRRs), followed by a double disulphide-bonded loop and an anionic sulphated region. This review summarizes recent research efforts elucidating the characteristics of the GPIb-vWF interaction. Potential mechanisms that regulate the GPIb-vWF function are discussed, and advances in identifying functional sequences within GPIba involved in the binding to vWF are reviewed.
authors.affiliation: Laboratory for Thrombosis Research, Interdisciplinary Research Center, Kortrijk, Belgium.
authors.forename: N
authors.initials: N
authors.lastname: Cauwenberghs
authors.forename: K
authors.initials: K
authors.lastname: Vanhoorelbeke
authors.forename: S
authors.initials: S
authors.lastname: Vauterin
authors.forename: H
authors.initials: H
authors.lastname: Deckmyn
mesh_terms: D000818:Animals; D006801:Humans; D010973:Platelet Adhesiveness / Q000502:physiology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D014841:von Willebrand Factor / Q000737:chemistry / Q000378:metabolism*
chemical_list: D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor