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Minimal collagen-binding epitope of glycoprotein VI in human and mouse platelets
Zitieren Sie bitte immer diese 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.…
Autor(en): | 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 |
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URN: | urn:nbn:de:bvb:20-opus-304148 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Fakultät für Biologie / Theodor-Boveri-Institut für Biowissenschaften |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Biomedicines |
ISSN: | 2227-9059 |
Erscheinungsjahr: | 2023 |
Band / Jahrgang: | 11 |
Heft / Ausgabe: | 2 |
Aufsatznummer: | 423 |
Originalveröffentlichung / Quelle: | Biomedicines (2023) 11:2, 423. https://doi.org/10.3390/biomedicines11020423 |
DOI: | https://doi.org/10.3390/biomedicines11020423 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | GPVI; anti-thrombotic therapies; blood platelets; collagen; thrombosis |
Datum der Freischaltung: | 09.10.2023 |
Datum der Erstveröffentlichung: | 01.02.2023 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |