Department of Anatomy and Cell Biology, McGill University, Montréal, QC, Canada.
Department of Cellular Biology, University of Georgia, Athens, GA, USA.
EMBO Rep. 2021 Sep 6;22(9):e52911. doi: 10.15252/embr.202152911. Epub 2021 Aug 2.
Cilia are thin microtubule-based protrusions of eukaryotic cells. The swimming of ciliated protists and sperm cells is propelled by the beating of cilia. Cilia propagate the flow of mucus in the trachea and protect the human body from viral infections. The main force generators of ciliary beating are the outer dynein arms (ODAs) which attach to the doublet microtubules. The bending of cilia is driven by the ODAs' conformational changes caused by ATP hydrolysis. Here, we report the native ODA complex structure attaching to the doublet microtubule by cryo-electron microscopy. The structure reveals how the ODA complex is attached to the doublet microtubule via the docking complex in its native state. Combined with coarse-grained molecular dynamic simulations, we present a model of how the attachment of the ODA to the doublet microtubule induces remodeling and activation of the ODA complex.
纤毛是真核细胞的一种基于微管的细小突起。纤毛虫和精子细胞的游动是由纤毛的摆动推动的。纤毛促进了气管中黏液的流动，并保护人体免受病毒感染。纤毛摆动的主要力发生器是附着在双联微管上的外动力蛋白臂（ODA）。纤毛的弯曲是由 ATP 水解引起的 ODA 构象变化驱动的。在这里，我们通过冷冻电子显微镜报告了附着在双联微管上的天然 ODA 复合物结构。该结构揭示了 ODA 复合物在其天然状态下如何通过对接复合物附着在双联微管上。结合粗粒分子动力学模拟，我们提出了一个模型，说明 ODA 与双联微管的结合如何诱导 ODA 复合物的重塑和激活。
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