Structure-function relationship of the platelet glycoprotein VI (GPVI) receptor: does it matter if it is a dimer or monomer?

J.C. Clark, F.N. Damaskinaki, Y.F.H. Cheung, A. Slater, S.P. Watson*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

4 Citations (Web of Science)

Abstract

GPVI is a critical signaling receptor responsible for collagen-induced platelet activation and a promising anti-thrombotic target in conditions such as coronary artery thrombosis, ischemic stroke, and atherothrombosis. This is due to the ability to block GPVI while having minimal effects on hemostasis, making it a more attractive target over current dual-antiplatelet therapy (DAPT) with acetyl salicylic acid and P2Y(12) inhibitors where bleeding can be a problem. Our current understanding of how the structure of GPVI relates to function is inadequate and recent studies contradict each other. In this article, we summarize the structure-function relationships underlying the activation of GPVI by its major ligands, including collagen, fibrin(ogen), snake venom toxins and charged exogenous ligands such as diesel exhaust particles. We argue that contrary to popular belief dimerization of GPVI is not required for binding to collagen but serves to facilitate binding through increased avidity, and that GPVI is expressed as a mixture of monomers and dimers on resting platelets, with binding of multivalent ligands inducing higher order clustering.
Original languageEnglish
Pages (from-to)724-732
Number of pages9
JournalPlatelets
Volume32
Issue number6
Early online date26 Feb 2021
DOIs
Publication statusPublished - 18 Aug 2021

Keywords

  • dimerization
  • gpvi
  • ligands
  • platelets
  • structure-function
  • Ligands
  • Platelets
  • GPVI
  • Dimerization
  • Structure-function

Cite this