Authors
T Bartossek4; N G Jones4; C Schäfer3; H Mott1; M Brennich2; C Kisker3; M Carrington1; M Engstler4;
1 Department of Biochemistry, University of Cambridge; 2 European Synchrotron Radiation Facility, Grenoble, France; 3 Lehrstuhl für Strukturbiologie, Rudolf-Virchow-Zentrum der Universität Würzburg, Germany; 4 Lehrstuhl für Zell- und Entwicklungsbiologie, Biozentrum der Universität Würzburg, Germany
Discussion
Trypanosoma brucei is protected from immune attack by the densely
packed and highly mobile variant surface glycoprotein (VSG) coat.
Despite its importance for parasite survival, no complete structure of
any VSG has been solved to date and the structure-function relationship
remains largely unknown. We employ small angle x-ray scattering (SAXS)
in combination with high-resolution domain structures of VSGs MITat1.1
and ILTat1.24 to solve the first complete VSG structures. The models are
based on crystal structures of the N-terminal domain and NMR-structures
of the C-terminal domain (CTD). Both VSGs show extensive flexibility
of the CTD and the domain linker, suggesting that VSGs can adopt relaxed
and compact conformations. This allows adaptive responses to obstacles
or changes in protein density, while maintaining the function of the VSG
coat as an impervious shield. Although the CTD-types of VSGs MITat1.1
and ILTat1.24 influence the overall membrane occupancy of the proteins,
relaxed and compact conformations exist for both VSGs. Our findings
emphasise the importance of the structural flexibility of the VSG in
maintaining a functional trypanosome surface coat.
