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Crystal structure of the factor XI zymogen reveals a pathway for transactivation

Nature Structural & Molecular Biology volume 13, pages 557–558 (2006)Cite this article

Abstract

Factor XI (FXI), a coagulation protein essential to normal hemostasis, circulates as a disulfide-linked dimer. Here we report the full-length FXI zymogen crystal structure, revealing that the protease and four apple domains assemble into a unique 'cup and saucer' architecture. The structure shows that the thrombin and platelet glycoprotein Ib binding sites are remote within the monomer but lie in close proximity across the dimer, suggesting a transactivation mechanism.

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Figure 1: FXI structure.
Figure 2: FXI activation.

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References

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Acknowledgements

We are grateful to E. Mitchell at European Synchrotron Research Facility beamline ID23 for assistance in data collection. This work was funded by grants from the US National Institutes of Health (RO1 HL46213, PO1 HL74124, Project 3) to P.N.W. and from the British Heart Foundation (PG/04/129/18095) and the Wellcome Trust (072975) to J.E.

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Authors and Affiliations

  1. Centre for Biomolecular Sciences, School of Pharmacy, University of Nottingham, Nottingham, NG72RD, UK

    Evangelos Papagrigoriou, Paul A McEwan & Jonas Emsley

  2. Department of Biochemistry, Department of Medicine, Sol Sherry Thrombosis Research Center, Fels Institute for Cancer Research, Temple University School of Medicine, Philadelphia, 19140, Pennsylvania, USA

    Peter N Walsh

Authors
  1. Evangelos Papagrigoriou
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  2. Paul A McEwan
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  3. Peter N Walsh
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  4. Jonas Emsley
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Contributions

E.P. performed crystallization, structure determination and model building. P.A.M. performed model refinement. P.N.W. contributed FXI protein samples. J.E. contributed to each stage of the research.

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Correspondence to Jonas Emsley.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Stereo diagrams of the FXI structure and representative electron density (PDF 664 kb)

Supplementary Fig. 2

FXI interdomain contacts (PDF 764 kb)

Supplementary Fig. 3

Charged surface representation of the FXI dimer (PDF 461 kb)

Supplementary Table 1

Data collection and refinement statistics (PDF 88 kb)

Supplementary Methods (PDF 103 kb)

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Papagrigoriou, E., McEwan, P., Walsh, P. et al. Crystal structure of the factor XI zymogen reveals a pathway for transactivation. Nat Struct Mol Biol 13, 557–558 (2006). https://doi.org/10.1038/nsmb1095

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