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001-es BibID:BIBFORM088736
035-os BibID:(cikkazonosító)112877
Első szerző:Szabó Gábor (PhD-hallgató)
Cím:Distinct and overlapping effects of [beta]2-glycoprotein I conformational variants in ligand interactions and functional assays / Szabó Gábor, Pénzes Krisztina, Torner Bernadett, Fagyas Miklós, Tarr Tünde, Soltész Pál, Kis Gréta, Antal Miklós, Kappelmayer János
Dátum:2020
ISSN:0022-1759
Megjegyzések:One of the most abundant coagulation proteins is ?2-glycoprotein I (?2GPI) that is present in humans at a concentration of around 200 mg/L. Its physiological role is only partially understood, but it adopts several different structural forms the majority of which are the open and closed forms. We isolated native (circular) ?2GPI and converted it into an open conformation. The effectiveness of these procedures was assessed by Western blot and negative-staining electron microscopy. We found that in coagulation assays the open form of ?2GPI had a significant prolonging effect on fibrin formation in a dilute prothrombin time test (p < 0.001). In the dilute activated partial thromboplastin time test, both conformations had a significant prolonging effect (p < 0.001) but the open conformation was more effective. In a fluorescent thrombin generation assay both conformations slightly delayed thrombin generation with no significant effect on the quantity of formed thrombin. By using surface plasmon resonance assays, the equilibrium dissociation constants of both the open and closed conformations of ?2GPI showed a similar and strong affinity to isolated anti-?2GPI autoantibodies (Kd closed ?2GPI = 5.17 ? 10-8 M, Kd open ?2GPI = 5.56 ? 10-8 M) and the open form had one order of magnitude stronger affinity to heparin (Kd = 0.30 ? 10-6 M) compared to the closed conformation (Kd = 3.50 ? 10-6 M). The two different forms of ?2GPI have distinct effects in functional tests and in ligand binding, which may considerably affect the intravascular events related to this abundant plasma protein in health and disease.
Tárgyszavak:Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Anti-[beta](2)-glycoprotein I
Heparin
Surface plasmon resonance
Thrombin generation
[beta](2)-glycoprotein I conformations
Megjelenés:Journal of Immunological Methods. - 487 (2020), p. 112877. -
További szerzők:Pénzes-Daku Krisztina (1978-) (biológus) Torner Bernadett (1997-) (molekuláris biológus) Fagyas Miklós (1984-) (orvos) Tarr Tünde (1976-) (belgyógyász, allergológus és klinikai immunológus) Soltész Pál (1961-) (belgyógyász, kardiológus) Kis Gréta (1979-) (molekuláris biológus) Antal Miklós (1951-) (orvos, anatómus) Kappelmayer János (1960-) (laboratóriumi szakorvos)
Pályázati támogatás:OTKA K16 120725
OTKA
GINOP-2.3.2-15-2016-00043
GINOP
Internet cím:Szerző által megadott URL
DOI
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