TY - JOUR
T1 - Structure-function relationship of the platelet glycoprotein VI (GPVI) receptor
T2 - does it matter if it is a dimer or monomer?
AU - Clark, Joanne C.
AU - Damaskinaki, Foteini-Nafsika
AU - Cheung, Yam Fung Hilaire
AU - Slater, Alexandre
AU - Watson, Steve P.
PY - 2021/8/18
Y1 - 2021/8/18
N2 - 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 P2Y12 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.
AB - 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 P2Y12 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.
KW - GPVI
KW - Dimerization
KW - Platelets
KW - Ligands
KW - Structure-function
U2 - 10.1080/09537104.2021.1887469
DO - 10.1080/09537104.2021.1887469
M3 - Article
SN - 0953-7104
VL - 32
SP - 724
EP - 732
JO - Platelets
JF - Platelets
IS - 6
ER -