  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.
