The most prominent defence of the unicellular parasite Trypanosoma brucei against the host immune system is a dense coat that comprises a variant surface glycoprotein (VSG). Despite the importance of the VSG family, no complete structure of a VSG has been reported. Making use of high-resolution structures of individual VSG domains, we employed small-angle X-ray scattering to elucidate the first two complete VSG structures. The resulting models imply that the linker regions confer great flexibility between domains, which suggests that VSGs can adopt two main conformations to respond to obstacles and changes of protein density, while maintaining a protective barrier at all times. Single-molecule diffusion measurements of VSG in supported lipid bilayers substantiate this possibility, as two freely diffusing populations could be detected. This translates into a highly flexible overall topology of the surface VSG coat, which displays both lateral movement in the plane of the membrane and variation in the overall thickness of the coat.

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This work was supported by the Deutsche Forschungsgemeinschaft (DFG, grants EN 305, GRK 1114 to M.E. and SFB 630 to M.E. and C.K.), and the Wellcome Trust (grant 022758/Z/03/Z to M.Ca.). A.-S.S. and M.Cv. were funded from grant ERC StG 2013-337283 of the European Research Council and supported by the DFG GRK 1962. M.E. is a member of the Wilhelm Conrad Röntgen-Center for Complex Material Systems. We thank the Helmholtz-Zentrum Berlin for the allocation of synchrotron radiation beamtime and the staff of the BESSY at beamline 14.1 for technical assistance. The SAXS experiments were performed on beamline BM29 at ESRF. We are grateful to A. Round at the ESRF for providing assistance in using beamline BM29 and for invaluable tips concerning data analysis. We thank D. Nietlispach for the acquisition of NMR data and B. Morriswood for critical reading of the manuscript.

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Author notes

    • Martha Brennich

    Present address: European Molecular Biology Laboratory, 71 Avenue des Martyrs, BP 181, 38042, Grenoble, France

  1. Thomas Bartossek and Nicola G. Jones contributed equally to this work.


  1. Department of Cell and Developmental Biology, Theodor-Boveri-Institute, Biocenter, University of Würzburg, 97074, Würzburg, Germany

    • Thomas Bartossek
    • , Nicola G. Jones
    • , Marius Glogger
    • , Susanne Fenz
    •  & Markus Engstler
  2. Rudolf Virchow Center for Experimental Biomedicine, Institute for Structural Biology, University of Würzburg, 97080, Würzburg, Germany

    • Christin Schäfer
    • , Jochen Kuper
    •  & Caroline Kisker
  3. PULS Group, Institut für Theoretische Physik and the Excellence Cluster: Engineering of Advanced Materials, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91052, Erlangen, Germany

    • Mislav Cvitković
    •  & Ana-Sunčana Smith
  4. Group for Computational Life Sciences, Division of Physical Chemistry, Ruđer Bošković Institute, 10000, Zagreb, Croatia

    • Mislav Cvitković
    •  & Ana-Sunčana Smith
  5. Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, UK

    • Helen R. Mott
    •  & Mark Carrington
  6. European Synchrotron Radiation Facility, 71 Avenue des Martyrs, CS 40220, 38042, Grenoble, France

    • Martha Brennich


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T.B., N.G.J. and M.E. conceived the study, T.B., N.G.J., M.Ca., A.-A.S., S.F., C.K. and M.E. designed the research; T.B., N.G.J., M.G. and S.F. performed the experiments; T.B., N.G.J., C.S., M.Cv., M.G., H.R.M., J.K., M.B., A.-S.S., S.F. and M.E. analysed the data; T.B., N.G.J. and M.E. wrote the paper with contributions from M.Cv., A.-S.S. and S.F. during manuscript editing.

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The authors declare no competing financial interests.

Corresponding authors

Correspondence to Nicola G. Jones or Markus Engstler.

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