Unravelling the mechanism and significance of thrombin binding to platelet glycoprotein Ib

• Published in: Thrombosis and haemostasis Vol. 104; no. 5; p. 894
• Main Authors: Ruggeri, Zaverio M, Zarpellon, Alessandro, Roberts, James R, Mc Clintock, Richard A, Jing, Hua, Mendolicchio, G Loredana
• Format: Journal Article
• Language: English
• Published: Germany 01.11.2010
• Subjects: Amino Acid Sequence; Animals; Binding Sites; Crystallography, X-Ray; Hemostasis; History, 20th Century; Humans; Models, Molecular; Molecular Sequence Data; Platelet Glycoprotein GPIb-IX Complex - chemistry; Platelet Glycoprotein GPIb-IX Complex - metabolism; Protein Conformation; Protein Interaction Domains and Motifs; Protein Interaction Mapping; Structure-Activity Relationship; Thrombin - chemistry; Thrombin - metabolism; Thrombosis - blood; Thrombosis - history; von Willebrand Factor - metabolism
• ISSN: 0340-6245
• DOI: 10.1160/TH10-09-0578

The main question concerning the mechanism of a-thrombin binding to platelet membrane glycoprotein (GP)Ib is whether it involves both thrombin exosite I and exosite II. The solution of two independent crystal structures suggests alternative explanations that may actually reflect different modes of binding with distinct pathophysiological significance. With respect to function, it is still unclear whether thrombin binding to GPIb promotes procoagulant and prothrombotic pathways of response to vascular injury or limits such responses by sequestering, at least temporarily, the active enzyme. We review here published information on these topics and touch upon ongoing studies aimed at finding definitive answers to outstanding questions relevant for a better understanding of thrombosis and haemostasis.