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

Zaverio M. Ruggeri, Alessandro Zarpellon, James R. Roberts, Richard A. Mc Clintock, Hua Jing, G. Loredana Mendolicchio

Research output: Contribution to journalArticle

Abstract

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 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.

Original languageEnglish
Pages (from-to)894-902
Number of pages9
JournalThrombosis and Haemostasis
Volume104
Issue number5
DOIs
Publication statusPublished - Nov 2010

Fingerprint

Platelet Glycoprotein GPIb-IX Complex
Platelet Membrane Glycoproteins
Thrombin
Vascular System Injuries
Hemostasis
Thrombosis
Enzymes

Keywords

  • Animal models
  • GPIb
  • Thrombin
  • Thrombosis
  • Von Willebrand factor

ASJC Scopus subject areas

  • Hematology

Cite this

Ruggeri, Z. M., Zarpellon, A., Roberts, J. R., Mc Clintock, R. A., Jing, H., & Mendolicchio, G. L. (2010). Unravelling the mechanism and significance of thrombin binding to platelet glycoprotein Ib. Thrombosis and Haemostasis, 104(5), 894-902. https://doi.org/10.1160/TH10-09-0578

Unravelling the mechanism and significance of thrombin binding to platelet glycoprotein Ib. / Ruggeri, Zaverio M.; Zarpellon, Alessandro; Roberts, James R.; Mc Clintock, Richard A.; Jing, Hua; Mendolicchio, G. Loredana.

In: Thrombosis and Haemostasis, Vol. 104, No. 5, 11.2010, p. 894-902.

Research output: Contribution to journalArticle

Ruggeri, ZM, Zarpellon, A, Roberts, JR, Mc Clintock, RA, Jing, H & Mendolicchio, GL 2010, 'Unravelling the mechanism and significance of thrombin binding to platelet glycoprotein Ib', Thrombosis and Haemostasis, vol. 104, no. 5, pp. 894-902. https://doi.org/10.1160/TH10-09-0578
Ruggeri ZM, Zarpellon A, Roberts JR, Mc Clintock RA, Jing H, Mendolicchio GL. Unravelling the mechanism and significance of thrombin binding to platelet glycoprotein Ib. Thrombosis and Haemostasis. 2010 Nov;104(5):894-902. https://doi.org/10.1160/TH10-09-0578
Ruggeri, Zaverio M. ; Zarpellon, Alessandro ; Roberts, James R. ; Mc Clintock, Richard A. ; Jing, Hua ; Mendolicchio, G. Loredana. / Unravelling the mechanism and significance of thrombin binding to platelet glycoprotein Ib. In: Thrombosis and Haemostasis. 2010 ; Vol. 104, No. 5. pp. 894-902.
@article{9b4918a7e3804e8ebd9091bfaa8fbcb8,
title = "Unravelling the mechanism and significance of thrombin binding to platelet glycoprotein Ib",
abstract = "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 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.",
keywords = "Animal models, GPIb, Thrombin, Thrombosis, Von Willebrand factor",
author = "Ruggeri, {Zaverio M.} and Alessandro Zarpellon and Roberts, {James R.} and {Mc Clintock}, {Richard A.} and Hua Jing and Mendolicchio, {G. Loredana}",
year = "2010",
month = "11",
doi = "10.1160/TH10-09-0578",
language = "English",
volume = "104",
pages = "894--902",
journal = "Thrombosis and Haemostasis",
issn = "0340-6245",
publisher = "Schattauer GmbH",
number = "5",

}

TY - JOUR

T1 - Unravelling the mechanism and significance of thrombin binding to platelet glycoprotein Ib

AU - Ruggeri, Zaverio M.

AU - Zarpellon, Alessandro

AU - Roberts, James R.

AU - Mc Clintock, Richard A.

AU - Jing, Hua

AU - Mendolicchio, G. Loredana

PY - 2010/11

Y1 - 2010/11

N2 - 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 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.

AB - 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 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.

KW - Animal models

KW - GPIb

KW - Thrombin

KW - Thrombosis

KW - Von Willebrand factor

UR - http://www.scopus.com/inward/record.url?scp=78149478342&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=78149478342&partnerID=8YFLogxK

U2 - 10.1160/TH10-09-0578

DO - 10.1160/TH10-09-0578

M3 - Article

C2 - 20941453

AN - SCOPUS:78149478342

VL - 104

SP - 894

EP - 902

JO - Thrombosis and Haemostasis

JF - Thrombosis and Haemostasis

SN - 0340-6245

IS - 5

ER -