A model for the unique role of factor Va A2 domain extension in the human ternary thrombin-generating complex

Biophysical Chemistry
Joong-Youn ShimLee G Pedersen

Abstract

An all-atom human ternary model for the prothrombinase-prothrombin complex, including metal ions and post-translationally modified residues, was constructed from existing X-ray crystal structures. The factor Xa-prothrombin interface was taken from an existing ternary model, which locates the active site of factor Xa in the vicinity of prothrombin cleavage positions. The three sulfotyrosine residues at the C-terminal sequence of factor Va A2 domain are accommodated by modelling rational interactions with positively charged patches on the surface of prothrombin. The entire model is then solvent-equilibrated with molecular dynamics. This ternary model for the thrombin-generating complex provides an estimate as to the role of the C-terminus of the factor Va A2 domain: to establish an interface between FXa and prothrombin and to stabilize the orientation of this interface.

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Citations

May 31, 2015·Biophysical Chemistry·Sangwook WuLee G Pedersen
Nov 26, 2015·The Journal of Biological Chemistry·Joesph R WiencekMichael Kalafatis
Jan 15, 2016·The Journal of Biological Chemistry·Nicola PozziEnrico Di Cera
May 19, 2019·Journal of Thrombosis and Haemostasis : JTH·Mark SchreuderMettine H A Bos
Jun 4, 2021·Blood·Josefin Ahnström
Mar 9, 2021·Blood·Eliza A RubenEnrico Di Cera
Jun 25, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Mark SchreuderMettine H A Bos

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