GPVI (Glycoprotein VI) Interaction With Fibrinogen Is Mediated by Avidity and the Fibrinogen αC-Region
| العنوان: | GPVI (Glycoprotein VI) Interaction With Fibrinogen Is Mediated by Avidity and the Fibrinogen αC-Region |
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| المؤلفون: | Cédric Duval, Robert A. S. Ariëns, Rui-Gang Xu, Helen R. McPherson, Iain W. Manfield, Alexandre Slater, Steve P. Watson, Stephen R. Baker, Julia S. Gauer, Eleyna M. Martin, Arkadiusz Bonna |
| المصدر: | Arteriosclerosis, Thrombosis, and Vascular Biology |
| بيانات النشر: | Ovid Technologies (Wolters Kluwer Health), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Platelet Aggregation, Platelet aggregation, Platelet Membrane Glycoproteins, In Vitro Techniques, 030204 cardiovascular system & hematology, Microscopy, Atomic Force, Fibrinogen, Fibrin, Fibrin Fibrinogen Degradation Products, glycoprotein VI, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Humans, Protein Interaction Domains and Motifs, Avidity, Platelet, fibrin, Protein Structure, Quaternary, thrombosis, chemistry.chemical_classification, biology, Basic Sciences, Surface Plasmon Resonance, Peptide Fragments, Cell biology, 030104 developmental biology, chemistry, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, biology.protein, GPVI, Carrier Proteins, Peptides, Cardiology and Cardiovascular Medicine, Glycoprotein, Signal Transduction, medicine.drug |
| الوصف: | Supplemental Digital Content is available in the text. Objective: GPVI (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. Conclusions: Based 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. |
| وصف الملف: | application/pdf |
| تدمد: | 1524-4636 1079-5642 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::364de8c6c649062c5b9fd9913ad664be https://doi.org/10.1161/atvbaha.120.315030 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....364de8c6c649062c5b9fd9913ad664be |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15244636 10795642 |
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