Skip to main content
SpringerLink
Log in

Backbone resonance assignments of the C2 domain of coagulation factor VIII

  • Article
  • Published:
Biomolecular NMR Assignments Aims and scope Submit manuscript

Abstract

Factor VIII (FVIII, other clotting factors are named similarly) is a glycoprotein that circulates in the plasma bound to von Willebrand factor. During the blood coagulation cascade, activated FVIII (FVIIIa) binds to FIXa and activates FX in the presence of calcium ions and phospholipid membranes. The C1 and C2 domains mediate membrane binding that is essential for activation of the FVIIIa–FIXa complex. Here, 1H, 13C, and 15N backbone chemical shift assignments are reported for the C2 domain of FVIII, including assignments for the residues in solvent-exposed loops. The NMR resonance assignments, along with further structural studies of membrane-bound FVIII, will advance understanding of blood-clotting protein interactions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Berjanskii MV, Wishart DS (2005) A simple method to predict protein flexibility using secondary chemical shifts. J Am Chem Soc 127:14970–14971

    Article  Google Scholar 

  • Delaglio F, Grzesiek S, Vuister GW, Zhu G, Pfeifer J, Bax A (1995) Nmrpipe: a multidimensional spectral processing system based on unix pipes. J Biomol NMR 6:277–293

    Article  Google Scholar 

  • Goddard TD, Kneller DG (2006) Sparky 3. University of California, San Francisco

    Google Scholar 

  • Kabsch W, Sander C (1983) Dictionary of protein secondary structure: pattern recognition of hydrogen-bonded and geometrical features. Biopolymers 22:2577–2637

    Article  Google Scholar 

  • Liu Z, Lin L, Yuan C, Nicolaes GAF, Chen L, Meehan EJ, Furie B, Furie B, Huang M (2010) Trp2313-His2315 of factor VIII C2 domain is involved in membrane binding. J Biol Chem 285:8824–8829

    Article  Google Scholar 

  • Novakovic VA, Cullinan DB, Wakabayashi H, Fay PJ, Baleja JD, Gilbert GE (2011) Membrane-binding properties of the factor VIII C2 domain. Biochem J 435:187–196

    Article  Google Scholar 

  • Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera- a visualization system for exploratory research and analysis. J Comput Chem 25:1605–1612

    Article  Google Scholar 

  • Pratt KP, Shen BW, Takeshima K, Davie EW, Fujikawa K, Stoddard BL (1999) Structure of the C2 domain of human factor VIII at 1.5 Å resolution. Nature 402:439–442

    Article  ADS  Google Scholar 

  • Shen Y, Delaglio F, Cornilescu G, Bax A (2009) TALOS plus: a hybrid method for predicting protein backbone torsion angles from NMR chemical shifts. J Biomol NMR 44:213–223

    Article  Google Scholar 

  • White GC, Shoemaker CB (1989) Factor VIII gene and hemophilia A. Blood 73:1–12

    Google Scholar 

Download references

Acknowledgments

This work was supported by National Institutes of Health grant P01HL42443 (to JDB), National Institutes of Health grant R01HL103999 (to CMR), and the Research Service of the Veterans Administration (GEG). Fellowship support was provided by a National Science Foundation Graduate Research Fellowship to KMN. KMN wishes to thank Gemma Comellas and Dr. Anna E. Nesbitt for insightful discussions.

Author information

Authors and Affiliations

  1. Department of Chemistry, University of Illinois at Urbana-Champaign, 600 S Mathews Ave, Urbana, IL, 61801, USA

    Kristin M. Nuzzio, John M. Boettcher & Chad M. Rienstra

  2. Department of Medicine, Veterans Affairs Boston Healthcare System, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, 02132, USA

    David B. Cullinan, Valerie A. Novakovic & Gary E. Gilbert

  3. Center for Biophysics and Computational Biology, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Chad M. Rienstra

  4. Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Chad M. Rienstra

  5. Department of Biochemistry, Tufts University School of Medicine, Boston, MA, 02111, USA

    James D. Baleja

Authors
  1. Kristin M. Nuzzio
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David B. Cullinan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Valerie A. Novakovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. John M. Boettcher
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chad M. Rienstra
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Gary E. Gilbert
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. James D. Baleja
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to James D. Baleja.

Additional information

Kristin M. Nuzzio and David B. Cullinan contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nuzzio, K.M., Cullinan, D.B., Novakovic, V.A. et al. Backbone resonance assignments of the C2 domain of coagulation factor VIII. Biomol NMR Assign 7, 31–34 (2013). https://doi.org/10.1007/s12104-012-9370-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12104-012-9370-5

Keywords

Search

Navigation