Minimal collagen-binding epitope of glycoprotein VI in human and mouse platelets

Please always quote using this URN: urn:nbn:de:bvb:20-opus-304148
  • Glycoprotein VI (GPVI) is a platelet-specific receptor for collagen and fibrin, regulating important platelet functions such as platelet adhesion and thrombus growth. Although the blockade of GPVI function is widely recognized as a potent anti-thrombotic approach, there are limited studies focused on site-specific targeting of GPVI. Using computational modeling and bioinformatics, we analyzed collagen- and CRP-binding surfaces of GPVI monomers and dimers, and compared the interacting surfaces with other mammalian GPVI isoforms. We could predictGlycoprotein VI (GPVI) is a platelet-specific receptor for collagen and fibrin, regulating important platelet functions such as platelet adhesion and thrombus growth. Although the blockade of GPVI function is widely recognized as a potent anti-thrombotic approach, there are limited studies focused on site-specific targeting of GPVI. Using computational modeling and bioinformatics, we analyzed collagen- and CRP-binding surfaces of GPVI monomers and dimers, and compared the interacting surfaces with other mammalian GPVI isoforms. We could predict a minimal collagen-binding epitope of GPVI dimer and designed an EA-20 antibody that recognizes a linear epitope of this surface. Using platelets and whole blood samples donated from wild-type and humanized GPVI transgenic mice and also humans, our experimental results show that the EA-20 antibody inhibits platelet adhesion and aggregation in response to collagen and CRP, but not to fibrin. The EA-20 antibody also prevents thrombus formation in whole blood, on the collagen-coated surface, in arterial flow conditions. We also show that EA-20 does not influence GPVI clustering or receptor shedding. Therefore, we propose that blockade of this minimal collagen-binding epitope of GPVI with the EA-20 antibody could represent a new anti-thrombotic approach by inhibiting specific interactions between GPVI and the collagen matrix.show moreshow less

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Metadaten
Author: Chao Han, Pengxuan Ren, Medina Mamtimin, Linus Kruk, Edita Sarukhanyan, Chenyu Li, Hans-Joachim Anders, Thomas Dandekar, Irena Krueger, Margitta Elvers, Silvia Goebel, Kristin Adler, Götz Münch, Thomas Gudermann, Attila Braun, Elmina Mammadova-Bach
URN:urn:nbn:de:bvb:20-opus-304148
Document Type:Journal article
Faculties:Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften
Language:English
Parent Title (English):Biomedicines
ISSN:2227-9059
Year of Completion:2023
Volume:11
Issue:2
Article Number:423
Source:Biomedicines (2023) 11:2, 423. https://doi.org/10.3390/biomedicines11020423
DOI:https://doi.org/10.3390/biomedicines11020423
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:GPVI; anti-thrombotic therapies; blood platelets; collagen; thrombosis
Release Date:2023/10/09
Date of first Publication:2023/02/01
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International