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The structure of serum resistance-associated protein and its implications for human African trypanosomiasis.
Nature Microbiology ( IF 20.5 ) Pub Date : 2018-01-22 , DOI: 10.1038/s41564-017-0085-3
Sebastian Zoll 1 , Harriet Lane-Serff 1 , Shahid Mehmood 2 , Jonathan Schneider 1 , Carol V Robinson 2 , Mark Carrington 3 , Matthew K Higgins 1
Affiliation  

Only two trypanosome subspecies are able to cause human African trypanosomiasis. To establish an infection in human blood, they must overcome the innate immune system by resisting the toxic effects of trypanolytic factor 1 and trypanolytic factor 2 (refs. 1,2). These lipoprotein complexes contain an active, pore-forming component, apolipoprotein L1 (ApoL1), that causes trypanosome cell death 3 . One of the two human-infective subspecies, Trypanosoma brucei rhodesiense, differs from non-infective trypanosomes solely by the presence of the serum resistance-associated protein, which binds directly to ApoL1 and blocks its pore-forming capacity3-5. Since this interaction is the single critical event that renders T. b. rhodesiense human- infective, detailed structural information that allows identification of binding determinants is crucial to understand immune escape by the parasite. Here, we present the structure of serum resistance-associated protein and reveal the adaptations that occurred as it diverged from other trypanosome surface molecules to neutralize ApoL1. We also present our mapping of residues important for ApoL1 binding, giving molecular insight into this interaction at the heart of human sleeping sickness.

中文翻译:

血清抗药性相关蛋白的结构及其对人类非洲锥虫病的影响。

仅两个锥虫亚种能够引起人类非洲锥虫病。要在人血中建立感染,他们必须通过抵抗锥虫溶解因子1和锥虫溶解因子2的毒性作用来克服先天免疫系统(参考文献1,2)。这些脂蛋白复合物包含一个活跃的成孔成分,载脂蛋白L1(ApoL1),可导致锥虫细胞死亡3。两个人类感染性亚种之一的布氏锥虫锥虫与非感染性锥虫的区别仅在于血清抗性相关蛋白的存在,该蛋白直接与ApoL1结合并阻断其成孔能力3-5。由于此交互是呈现T的单个关键事件。罗得西亚人感染,允许鉴定结合决定簇的详细结构信息对于了解寄生虫的免疫逃逸至关重要。在这里,我们介绍了血清抗药性相关蛋白的结构,并揭示了它与其他锥虫表面分子中和ApoL1时发生的适应性变化。我们还提出了对ApoL1结合很重要的残基的定位图,从而使人们深入了解了人类昏睡病核心的这种相互作用。
更新日期:2018-01-22
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