Download PDF
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
1   CEA, iBEB, Service de Biochimie et Toxicologie Nucléaire, Bagnols sur Cèze, France
,
Selma Dahmane
1   CEA, iBEB, Service de Biochimie et Toxicologie Nucléaire, Bagnols sur Cèze, France
3   Present address: Inserm, Unité 1054, Single Molecule Biophysics Department, Centre de Biochimie Structurale, Montpellier, France
,
Michael Odorico
1   CEA, iBEB, Service de Biochimie et Toxicologie Nucléaire, Bagnols sur Cèze, France
,
Gerry A.F. Nicolaes
2   Department of Biochemistry, Cardiovascular Research Institute Maastricht, CARIM, Maastricht University, the Netherlands
,
Jean-Luc Pellequer
1   CEA, iBEB, Service de Biochimie et Toxicologie Nucléaire, Bagnols sur Cèze, France
4   New address: IBS, Univ. Grenoble Alpes/CNRS/CEA, 71 avenue des Martyrs CS 10090, F-38044 Grenoble, Cedex 9, France
› Author Affiliations Financial support: This work was initially supported by the Agence Nationale de la Recherche [ANR-07-PCVI-0002–01] and the Commissariat à l’énergie atomique et aux énergies alternatives (CEA).
Further Information

Publication History

Received: 01 June 2014

Accepted after major revision: 15 July 2014

Publication Date:
29 November 2017 (online)

    Permissions and Reprints

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

 

  • References

  • 1 Davie EW, Ratnoff OD. Waterfall sequence for intrinsic blood clotting. Science 1964; 145: 1310-1312.
    CrossrefPubMedGoogle Scholar
  • 2 MacFarlane RG. An enzyme cascade in the blood clotting mechanism, and its function as a biochemical amplifier. Nature 1964; 202: 498-499.
    CrossrefPubMedGoogle Scholar
  • 3 Dahlback B. Blood coagulation. Lancet 2000; 355: 1627-1632.
    CrossrefPubMedGoogle Scholar
  • 4 Esmon CT, Suttie JW, Jackson CM. The functional significance of vitamin K action. Difference in phospholipid binding between normal and abnormal prothrombin. J Biol Chem 1975; 250: 4095-4099.
    PubMedGoogle Scholar
  • 5 Kalafatis M, Rand MD, Mann KG. The mechanism of inactivation of human factor V and human factor Va by activated protein C. J Biol Chem 1994; 269: 31869-31880.
    PubMedGoogle Scholar
  • 6 Nicolaes GAF, Tans G, Thomassen MCLGD. et al. Peptide bond cleavages and loss of functional activity during inactivation of factor Va and factor VaR506Q by activated protein C. J Biol Chem 1995; 270: 21158-21166.
    CrossrefPubMedGoogle Scholar
  • 7 Bertina RM, Koeleman BPC, Koster T. et al. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature 1994; 369: 64-67.
    CrossrefPubMedGoogle Scholar
  • 8 Jenny RJ, Pittman DD, Toole JJ. et al. Complete cDNA and derived amino acid sequence of human factor V. Proc Natl Acad Sci USA 1987; 84: 4846-4850.
    CrossrefPubMedGoogle Scholar
  • 9 Adams TE, Hockin MF, Mann KG. et al. The crystal structure of activated protein C-inactivated bovine factor Va: Implications for cofactor function. Proc Natl Acad Sci USA 2004; 101: 8918-8923.
    CrossrefPubMedGoogle Scholar
  • 10 Nicolaes GA, Villoutreix BO, Dahlback B. Mutations in a potential phospholipid binding loop in the C2 domain of factor V affecting the assembly of the prothrombinase complex. Blood Coagul Fibrinolysis 2000; 11: 89-100.
    CrossrefPubMedGoogle Scholar
  • 11 Saleh M, Peng W, Quinn-Allen MA. et al. The factor V C1 domain is involved in membrane binding: identification of functionally important amino acid residues within the C1 domain of factor V using alanine scanning mutagenesis. Thromb Haemost 2004; 91: 16-27.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Peng W, Quinn-Allen MA, Kane WH. Mutation of hydrophobic residues in the factor Va C1 and C2 domains blocks membrane-dependent prothrombin activation. J Thromb Haemost 2005; 03: 351-354.
    CrossrefPubMedGoogle Scholar
  • 13 Pellequer JL, Gale AJ, Getzoff ED. et al. Three-dimensional model of the coagulation factor Va bound to activated protein C. Thromb Haemost 2000; 84: 849-857.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Villoutreix BO, Dahlback B. Structural investigation of the A domains of human blood coagulation factor V by molecular modeling. Protein Sci 1998; 07: 1317-1325.
    CrossrefPubMedGoogle Scholar
  • 15 Pellequer J-L, Gale AJ, Griffin JH. et al. Homology models of the C domains of blood coagulation factors V and VIII: A proposed membrane binding mode for FV and FVIII C2 domains. Blood Cells Mol Dis 1998; 24: 448-461.
    CrossrefPubMedGoogle Scholar
  • 16 Villoutreix BO, Bucher P, Hofmann K. et al. Molecular models for the two discoidin domains of human blood coagulation factor V. J Mol Model 1998; 04: 268-275.
    CrossrefPubMedGoogle Scholar
  • 17 Macedo-Ribeiro S, Bode W, Huber R. et al. Crystal structures of the membrane-binding C2 domain of human coagulation factor V. Nature 1999; 402: 434-439.
    CrossrefPubMedGoogle Scholar
  • 18 Orban T, Kalafatis M, Gogonea V. Completed three-dimensional model of human coagulation factor Va. Molecular dynamics simulations and structural analyses. Biochemistry 2005; 44: 13082-13090.
    CrossrefPubMedGoogle Scholar
  • 19 Autin L, Steen M, Dahlback B. et al. Proposed structural models of the prothrombinase (FXa-FVa) complex. Proteins 2006; 63: 440-450.
    CrossrefPubMedGoogle Scholar
  • 20 Gale AJ, Yegneswaran S, Xu X. et al. Characterization of a factor Xa binding site on factor Va near the Arg506 APC cleavage site. J Biol Chem 2007; 282: 21848-21855.
    CrossrefPubMedGoogle Scholar
  • 21 Lee CJ, Lin P, Chandrasekaran V. et al. Proposed structural models of human factor Va and prothrombinase. J Thromb Haemost 2008; 06: 83-89.
    PubMedGoogle Scholar
  • 22 Lechtenberg BC, Murray-Rust TA, Johnson DJ. et al. Crystal structure of the prothrombinase complex from the venom of Pseudonaja textilis. Blood 2013; 122: 2777-2783.
    CrossrefPubMedGoogle Scholar
  • 23 Zhou ZH. Towards atomic resolution structural determination by single-particle cryo-electron microscopy. Curr Opin Struct Biol 2008; 18: 218-228.
    CrossrefPubMedGoogle Scholar
  • 24 Stoilova-McPhie S, Parmenter CD, Segers K. et al. Defining the structure of membrane-bound human blood coagulation factor Va. J Thromb Haemost 2008; 06: 76-82.
    PubMedGoogle Scholar
  • 25 Shao Z. Probing nanometer structures with Atomic Force Microscopy. News Physiol Sci 1999; 14: 142-149.
    PubMedGoogle Scholar
  • 26 Scheuring S, Boudier T, Sturgis JN. From high-resolution AFM topographs to atomic models of supramolecular assemblies. J Struct Biol 2007; 159: 268-276.
    CrossrefPubMedGoogle Scholar
  • 27 Muller SA, Muller DJ, Engel A. Assessing the structure and function of single biomolecules with scanning transmission electron and atomic force microscopes. Micron 2011; 42: 186-195.
    CrossrefPubMedGoogle Scholar
  • 28 Chaves RC, Teulon J-M, Odorico M. et al. Conformational dynamics of individual antibodies using computational docking and AFM. J Mol Recognit 2013; 26: 596-604.
    CrossrefPubMedGoogle Scholar
  • 29 Fechner P, Boudier T, Mangenot S. et al. Structural information, resolution, and noise in high-resolution atomic force microscopy topographs. Biophys J 2009; 96: 3822-3831.
    CrossrefPubMedGoogle Scholar
  • 30 Chen S-wW, Odorico M, Meillan M. et al. Nanoscale structural features determined by AFM for single virus particles. Nanoscale 2013; 22: 10877-10886.
    PubMedGoogle Scholar
  • 31 Schabert FA, Engel A. Reproducible acquisition of Escherichia coli porin surface topographs by atomic force microscopy. Biophys J 1994; 67: 2394-2403.
    CrossrefPubMedGoogle Scholar
  • 32 Binnig G, Quate CF, Gerber C. Atomic force microscope. Phys Rev Lett 1986; 56: 930-933.
    CrossrefPubMedGoogle Scholar
  • 33 Chen S-wW, Pellequer JL. DeStripe: frequency-based algorithm for removing stripe noises from AFM images. BMC Struct Biol 2011; 11: 7.
    CrossrefPubMedGoogle Scholar
  • 34 Trinh M-H, Odorico M, Bellanger L. et al. Tobacco mosaic virus as an AFM tip calibrator. J Mol Recognit 2011; 24: 503-510.
    CrossrefPubMedGoogle Scholar
  • 35 Chen S-wW, Pellequer JL. Adepth: new representation and its implications for atomic depths of macromolecules. Nucl Acids Res 2013; 41: W412-W416.
    CrossrefPubMedGoogle Scholar
  • 36 Trinh M-H, Odorico M, Pique ME. et al. Computational reconstruction of multidomain proteins using atomic force microscopy data. Structure 2012; 20: 113-120.
    CrossrefPubMedGoogle Scholar
  • 37 Ortel TL, Devore-Carter D, Quinn-Allen MA. et al. Deletion analysis of recombinant human factor V. Evidence for a phosphatidylserine binding site in the second C-type domain. J Biol Chem 1992; 267: 4189-4198.
    PubMedGoogle Scholar
  • 38 Kalafatis M, Jenny RJ, Mann KG. Identification and characterization of a phospholipid-binding site of bovine factor Va. J Biol Chem 1990; 265: 21580-21589.
    PubMedGoogle Scholar
  • 39 Kalafatis M, Rand MD, Mann KG. Factor Va-membrane interaction is mediated by two regions located on the light chain of the cofactor. Biochemistry 1994; 33: 486-493.
    CrossrefPubMedGoogle Scholar
  • 40 Majumder R, Quinn-Allen MA, Kane WH. et al. A phosphatidylserine binding site in factor Va C1 domain regulates both assembly and activity of the prothrombinase complex. Blood 2008; 112: 2795-2802.
    CrossrefPubMedGoogle Scholar
  • 41 Ngo JC, Huang M, Roth DA. et al. Crystal structure of human factor VIII: implications for the formation of the factor IXa-factor VIIIa complex. Structure 2008; 16: 597-606.
    CrossrefPubMedGoogle Scholar
  • 42 Shen BW, Spiegel PC, Chang CH. et al. The tertiary structure and domain organization of coagulation factor VIII. Blood 2008; 111: 1240-1247.
    CrossrefPubMedGoogle Scholar
  • 43 Stoilova-McPhie S, Lynch GC, Ludtke S. et al. Domain organization of membrane-bound factor VIII. Biopolymers 2013; 99: 448-459.
    CrossrefPubMedGoogle Scholar
  • 44 Schneider SW, Larmer J, Henderson RM. et al. Molecular weights of individual proteins correlate with molecular volumes measured by atomic force microscopy. Pflugers Arch 1998; 435: 362-367.
    CrossrefPubMedGoogle Scholar
  • 45 Chen S-wW, Pellequer JL. Identification of functionally important residues in proteins using comparative models. Curr Med Chem 2004; 11: 595-605.
    CrossrefPubMedGoogle Scholar
  • 46 Bongini L, Fanelli D, Piazza F. et al. Freezing immunoglobulins to see them move. Proc Natl Acad Sci USA 2004; 101: 6466-6471.
    CrossrefPubMedGoogle Scholar
  • 47 Chaves RC, Pellequer JL. DockAFM: benchmarking protein structures by docking under AFM topographs. Bioinformatics 2013; 29: 3230-3231.
    CrossrefPubMedGoogle Scholar
  • 48 Humphrey W, Dalke A, Schulten K. VMD: visual molecular dynamics. J Mol Graph 1996; 14: 33-38.
    CrossrefPubMedGoogle Scholar