Factor Va alternative conformation reconstruction using atomic force microscopy

Rui C. Chaves; Selma Dahmane; Michael Odorico; Gerry A.F. Nicolaes; Jean-Luc Pellequer

doi:10.1160/th14-06-0481

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2014; 112(06): 1167-1173
DOI: 10.1160/th14-06-0481

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

Factor Va alternative conformation reconstruction using atomic force microscopy

Rui C. Chaves

¹CEA, iBEB, Service de Biochimie et Toxicologie Nucléaire, Bagnols sur Cèze, France

,

Selma Dahmane

¹CEA, iBEB, Service de Biochimie et Toxicologie Nucléaire, Bagnols sur Cèze, France

³Present address: Inserm, Unité 1054, Single Molecule Biophysics Department, Centre de Biochimie Structurale, Montpellier, France

,

Michael Odorico

¹CEA, iBEB, Service de Biochimie et Toxicologie Nucléaire, Bagnols sur Cèze, France

,

Gerry A.F. Nicolaes

²Department of Biochemistry, Cardiovascular Research Institute Maastricht, CARIM, Maastricht University, the Netherlands

,

Jean-Luc Pellequer

¹CEA, iBEB, Service de Biochimie et Toxicologie Nucléaire, Bagnols sur Cèze, France

⁴New address: IBS, Univ. Grenoble Alpes/CNRS/CEA, 71 avenue des Martyrs CS 10090, F-38044 Grenoble, Cedex 9, France

› Author Affiliations

Abstract

Summary

Protein conformational variability (or dynamics) for large macromolecules and its implication for their biological function attracts more and more attention. Collective motions of domains increase the ability of a protein to bind to partner molecules. Using atomic force microscopy (AFM) topographic images, it is possible to take snapshots of large multi-component macromolecules at the single molecule level and to reconstruct complete molecular conformations. Here, we report the application of a reconstruction protocol, named AFM-assembly, to characterise the conformational variability of the two C domains of human coagulation factor Va (FVa). Using AFM topographic surfaces obtained in liquid environment, it is shown that the angle between C1 and C2 domains of FVa can vary between 40° and 166°. Such dynamical variation in C1 and C2 domain arrangement may have important implications regarding the binding of FVa to phospholipid membranes.

Keywords

Coagulation factors - imaging - phospholipids - protein structure / folding - atomic force microscopy

Full Text

References

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