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Tuesday, July 28 • 17:05 - 17:10
Impact of genetic variation on the association rate constant of von Willebrand factor and GPIbα platelet receptor

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Von Willebrand factor (VWF) is a large multimeric protein involved in the processes of platelet adhesion and activation. A1-domain of von Willebrand factor subunit interacts with the complex GPIb-V-IX, a platelet transmembrane receptor complex, via the receptor GPIbα. 

Information concerning VWF and GPIbα genetic variation are available in open database ClinVar. In the present work we analysed the impact of genetic variation on the association rate constant of von Willebrand factor and GPIbα platelet receptor. Basing on the PDB-structures the rate constants ka of VWF-A1 and GPIbα association were determined for the series of genetic variations (Alsallq & Zhou, 2008). The work has been focused on the clinically significant genetic variants both of VWF-A1 and GPIbα (Landrum et al., 2018). 

It was found that certain mutations (Trp1313Cys, Arg1379Cys) in von Willebrand factor A1-domain caused several fold decrease, while the mutation (Gly249Val) is followed by significant increase of the association rate constant ka values.

Models of VWF A3-domain and collagen III interaction, as well as VWF A1-domain and bitiscetin interaction have been studied in the similar manner. Mutation Ser1783Ala in VWF A3-domain caused а nearly two-fold increase of the ka value in case of the interaction model with collagen III. 

The results obtained seem to be important for the interpretation of clinical data concerning Bernard-Soulier syndrome, von Willebrand disease (VWD) and pseudo-VWD.

The work has been supported by Russian Science Foundation (Grant 19-11-00260).

Speakers
avatar for Maria Gefen

Maria Gefen

National Research Center for Hematology & Moscow Institute of Physics and Technology


Tuesday July 28, 2020 17:05 - 17:10 MSK
Zoom Conference https://zoom.us/j/94321101353?pwd=QlJBb09uM0NVVnVyK0FkbTJ3Nkcrdz09