ArticleArteriosclerosis, thrombosis, and vascular biology2021
GPVI (Glycoprotein VI) Interaction With Fibrinogen Is Mediated by Avidity and the Fibrinogen αC-Region.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Platelet-Collagen Interactions in Hemostatic Mechanisms.Advanced healthcare materials · 2026Review
- The fibrinogen αC region promotes arterial thrombosis in the context of hypofibrinogenemia.Blood · 2026Article
- Receptor homodimerization significantly prolongs the lifetime of ligand-induced cross-linking of CLEC-2 but not GPVI.Blood vessels, thrombosis & hemostasis · 2026Article
- Research advances on platelet glycoprotein VI in ischemic stroke.Thrombosis journal · 2026Review
- Translational immunothrombosis in autoimmune Heparin-Induced thrombocytopenia: targeting the FcγRIIa-Syk-BTK and complement pathways.Clinical and experimental medicine · 2026Review
- Fibrin Monomer in Thrombosis and Haemostasis: A Clinical Biomarker and Beyond.International journal of molecular sciences · 2025Review
- Characterization of Novel Variants inBiomolecules · 2025Article
- Post-translational modifications of fibrinogen: implications for clotting, fibrin structure and degradation.Molecular biomedicine · 2024Review
- Mendelian Randomization and Bayesian Colocalization Analysis Implicate Glycoprotein VI as a Potential Drug Target for Cardioembolic Stroke in South Asian Populations.Journal of the American Heart Association · 2024Article
- GPVI inhibition: Advancing antithrombotic therapy in cardiovascular disease.European heart journal. Cardiovascular pharmacotherapy · 2024Review
- Affimer reagents as tool molecules to modulate platelet GPVI-ligand interactions and specifically bind GPVI dimer.Blood advances · 2024Article
- Why platelet mechanotransduction matters for hemostasis and thrombosis.Journal of thrombosis and haemostasis : JTH · 2023Review
- Protease-activated receptors and glycoprotein VI cooperatively drive the platelet component in thromboelastography.Journal of thrombosis and haemostasis : JTH · 2023Article
- Targeting platelet GPVI with glenzocimab: a novel mechanism for inhibition.Blood advances · 2023Article
- Should aspirin be replaced with ADP blockers and anti-GPVI to manage thrombosis?Vascular biology (Bristol, England) · 2023Review
- Platelets and tyrosine kinase inhibitors: clinical features, mechanisms of action, and effects on physiology.American journal of physiology. Cell physiology · 2022Review
- Modulation of Glycoprotein VI and Its Downstream Signaling Pathways as an Antiplatelet Target.International journal of molecular sciences · 2022Review
- Procoagulant platelet sentinels prevent inflammatory bleeding through GPIIBIIIA and GPVI.Blood · 2022Article
- Article
- Platelet GPVI (Glycoprotein VI) and Thrombotic Complications in the Venous System.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveGPVI (glycoprotein VI) is a key molecular player in collagen-induced platelet signaling and aggregation. Recent evidence indicates that it also plays important role in platelet aggregation and thrombus growth through interaction with fibrin(ogen). However, there are discrepancies in the literature regarding whether the monomeric or dimeric form of GPVI binds to fibrinogen at high affinity. The mechanisms of interaction are also not clear, including which region of fibrinogen is responsible for GPVI binding. We aimed to gain further understanding of the mechanisms of interaction at molecular level and to identify the regions on fibrinogen important for GPVI binding. Approach and Results: Using multiple surface- and solution-based protein-protein interaction methods, we observe that dimeric GPVI binds to fibrinogen with much higher affinity and has a slower dissociation rate constant than the monomer due to avidity effects. Moreover, our data show that the highest affinity interaction of GPVI is with the αC-region of fibrinogen. We further show that GPVI interacts with immobilized fibrinogen and fibrin variants at a similar level, including a nonpolymerizing fibrin variant, suggesting that GPVI binding is independent of fibrin polymerization.
conclusionsBased on the above findings, we conclude that the higher affinity of dimeric GPVI over the monomer for fibrinogen interaction is achieved by avidity. The αC-region of fibrinogen appears essential for GPVI binding. We propose that fibrin polymerization into fibers during coagulation will cluster GPVI through its αC-region, leading to downstream signaling, further activation of platelets, and potentially stimulating clot growth. Graphic Abstract: A graphic abstract is available for this article.
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