Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, United States.
Molecular Biology Institute, University of California, Los Angeles, Los Angeles, United States.
Elife. 2019 Nov 11;8:e52058. doi: 10.7554/eLife.52058.
The 96-nm axonemal repeat includes dynein motors and accessory structures as the foundation for motility of eukaryotic flagella and cilia. However, high-resolution 3D axoneme structures are unavailable for organisms among the Excavates, which include pathogens of medical and economic importance. Here we report cryo electron tomography structures of the 96-nm repeat from , a protozoan parasite in the Excavate lineage that causes African trypanosomiasis. We examined bloodstream and procyclic life cycle stages, and a knockdown lacking DRC11/CMF22 of the nexin dynein regulatory complex (NDRC). Sub-tomogram averaging yields a resolution of 21.8 Å for the 96-nm repeat. We discovered several lineage-specific structures, including novel inter-doublet linkages and microtubule inner proteins (MIPs). We establish that DRC11/CMF22 is required for the NDRC proximal lobe that binds the adjacent doublet microtubule. We propose that lineage-specific elaboration of axoneme structure in reflects adaptations to support unique motility needs in diverse host environments.
96nm 轴丝重复结构包含动力蛋白和附属结构，是真核鞭毛和纤毛运动的基础。然而，挖掘生物群中缺乏高分辨率的 3D 轴丝结构，这些生物包括具有医学和经济重要性的病原体。本文报道了 属原生动物寄生虫的 96nm 重复结构，该寄生虫引起非洲锥虫病。我们检测了血液和前鞭毛体生命循环阶段，以及缺失了连接蛋白动力蛋白调节复合物（NDRC）的 DRC11/CMF22 的敲低表型。亚断层平均得到了 21.8Å 的分辨率。我们发现了几个谱系特异性结构，包括新的内二联体连接和微管内蛋白（MIPs）。我们确定 DRC11/CMF22 对于结合相邻二联体微管的 NDRC 近端叶是必需的。我们提出，轴丝结构的谱系特异性修饰反映了在不同宿主环境中支持独特运动需求的适应性。
