Thromb Haemost 2010; 104(05): 894-902
DOI: 10.1160/TH10-09-0578
Theme Issue Article
Schattauer GmbH

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

Zaverio M. Ruggeri
1  Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
,
Alessandro Zarpellon
1  Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
,
James R. Roberts
1  Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
,
Richard A. Mc Clintock
1  Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
,
Hua Jing
1  Roon Research Center for Arteriosclerosis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California, USA
,
G. Loredana Mendolicchio
2  IRCCS Istituto Clinico Humanitas, Milan, Italy
› Author Affiliations
Further Information

Publication History

Received: 08 September 2010

Accepted: 21 September 2010

Publication Date:
24 November 2017 (online)

Summary

The main question concerning the mechanism of α-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 re-sponse 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.