Department of Cell and Developmental Biology, Theodor-Boveri-Institute, Biocenter, University of Würzburg, 97074, Würzburg, Germany.
Rudolf Virchow Center for Experimental Biomedicine, Institute for Structural Biology, University of Würzburg, 97080, Würzburg, Germany.
Nat Microbiol. 2017 Nov;2(11):1523-1532. doi: 10.1038/s41564-017-0013-6. Epub 2017 Sep 11.
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.
无细胞寄生虫锥虫（Trypanosoma brucei）抵御宿主免疫系统的最显著防御机制是一层由变异表面糖蛋白（VSG）组成的密集外壳。尽管 VSG 家族非常重要，但目前尚未报道完整的 VSG 结构。利用单个 VSG 结构域的高分辨率结构，我们利用小角度 X 射线散射技术阐明了前两个完整的 VSG 结构。结果模型表明，连接区在结构域之间赋予了极大的灵活性，这表明 VSG 可以采用两种主要构象来应对障碍物和蛋白质密度的变化，同时始终保持保护屏障。在支持的脂质双层中 VSG 的单分子扩散测量证实了这种可能性，因为可以检测到两种自由扩散的群体。这转化为表面 VSG 外壳的高度灵活的整体拓扑结构，其在膜的平面内显示出横向运动和外壳整体厚度的变化。
