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Structural models of FVIII:

1. Crystal structures of B-domainless FVIII: 2008

The hot news in structure function terms is the recent (2008) publication of two structures for B-domainless FVIII, from the Barry Stoddard and Bruce Furie groups.

1. Blood. 2008 Feb 1;111(3):1240-7. The tertiary structure and domain organization of coagulation factor VIII. Shen BW, Spiegel PC, Chang CH, Huh JW, Lee JS, Kim J, Kim YH, Stoddard BL. Program in Molecular Biophysics, Structure and Design, Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Go here for PDF.

2. Structure. 2008 Apr;16(4):597-606. Crystal Structure of Human Factor VIII: Implications for the Formation of the Factor IXa-Factor VIIIa Complex. Ngo JC, Huang M, Roth DA, Furie BC, Furie B. Marine Biological Laboratory, Woods Hole, MA 02543, USA. Go here for PDF.

2. Five-domain model of FVIII: 2002

February 2002 brought the availability of a five-domain model for factor VIII, constructed using the crystal structure for the C2 domain (K Pratt et al., 1999) together with homology models for the C1 domain (based on C2) and the A domain heterotrimer (based on the crystal structure of caeruloplasmin - see section 2 below for more details).

A description of the construction of the model and its implications has been published in Blood (Stoylova-McPhie et al, 2002). You can download this publication as a PDF file here although it has been superseded by the two BDD-FVIII crystal structures.

To download the 3D coordinates of the five-domain FVIII model in PDB format click here. You may use and distribute this model freely however we would be pleased to hear from you if you download it. Email geoffrey.kemball-cook@csc.mrc.ac.uk

3. Homology model of the A domains of FVIII: 1997

A1 domain: residues A1-R336

A2 domain: residues A375-Y719

A3 domain: residues F1691-L2025

We have constructed a molecular model of the triplicated A domains of human FVIII using the human caeruloplasmin crystal structure (Zaitseva et al, J Bioinorg Chem Vol 1, p15 (1996) as a template. Please find below several ways to work with the model.

Publication of the Model: A paper describing the model is published in BLOOD (1997, Vol 89 N0.7, p2413). For a selection of information related to the paper click here, or visit the BLOOD Website.

The coordinates in PDB format are now available.

Bioinformatics: We have used MSI INSIGHT II to calculate the secondary structure and fractional sidechain solvent accessibility for each residue in the factor VIII A domain homology model. For ease of use, the data are presented in three tables, each featuring one A domain.

  1. A1 domain (Factor VIII A1-R336)
  2. A2 domain (Factor VIII A375-Y719)
  3. A3 domain (Factor VIII F1691-L2025)

Sequence comparisons: We have added FVIII amino acid sequence information to the Structure page, with sequence from four species now available. A lineup showing conserved residues across human, porcine, canine and murine FVIII is included.