Evolutionary adaptations of doublet microtubules in trypanosomatid parasites

IF 45.8 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Science Pub Date : 2025-03-14
Matthew H. Doran, Qingwei Niu, Jianwei Zeng, Tom Beneke, James Smith, Peter Ren, Sophia Fochler, Adrian Coscia, Johanna L. Höög, Shimi Meleppattu, Polina V. Lishko, Richard J. Wheeler, Eva Gluenz, Rui Zhang, Alan Brown
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Abstract

The movement and pathogenicity of trypanosomatid species, the causative agents of trypanosomiasis and leishmaniasis, are dependent on a flagellum that contains an axoneme of dynein-bound doublet microtubules (DMTs). In this work, we present cryo–electron microscopy structures of DMTs from two trypanosomatid species, Leishmania tarentolae and Crithidia fasciculata, at resolutions up to 2.7 angstrom. The structures revealed 27 trypanosomatid-specific microtubule inner proteins, a specialized dynein-docking complex, and the presence of paralogous proteins that enable higher-order periodicities or proximal-distal patterning. Leveraging the genetic tractability of trypanosomatid species, we quantified the location and contribution of each structure-identified protein to swimming behavior. Our study shows that proper B-tubule closure is critical for flagellar motility, exemplifying how integrating structural identification with systematic gene deletion can dissect individual protein contributions to flagellar motility.

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锥虫寄生虫双微管的进化适应
锥虫病和利什曼病的病原体锥虫虫的运动和致病性依赖于含有动力蛋白结合的双联微管轴突(dmt)的鞭毛。在这项工作中,我们展示了两种锥虫物种,利什曼绦虫和束状棘虫的dmt的低温电镜结构,分辨率高达2.7埃。这些结构揭示了27个锥虫特有的微管内部蛋白,一个特殊的动力对接复合物,以及支持高阶周期性或近端-远端模式的旁系蛋白的存在。利用锥虫物种的遗传易变性,我们量化了每种结构鉴定蛋白对游泳行为的位置和贡献。我们的研究表明,适当的b小管关闭对鞭毛运动至关重要,这说明了如何将结构鉴定与系统基因缺失结合起来,可以解剖单个蛋白质对鞭毛运动的贡献。
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来源期刊
Science
Science 综合性期刊-综合性期刊
CiteScore
61.10
自引率
0.90%
发文量
0
审稿时长
2.1 months
期刊介绍: Science is a leading outlet for scientific news, commentary, and cutting-edge research. Through its print and online incarnations, Science reaches an estimated worldwide readership of more than one million. Science’s authorship is global too, and its articles consistently rank among the world's most cited research. Science serves as a forum for discussion of important issues related to the advancement of science by publishing material on which a consensus has been reached as well as including the presentation of minority or conflicting points of view. Accordingly, all articles published in Science—including editorials, news and comment, and book reviews—are signed and reflect the individual views of the authors and not official points of view adopted by AAAS or the institutions with which the authors are affiliated. Science seeks to publish those papers that are most influential in their fields or across fields and that will significantly advance scientific understanding. Selected papers should present novel and broadly important data, syntheses, or concepts. They should merit recognition by the wider scientific community and general public provided by publication in Science, beyond that provided by specialty journals. Science welcomes submissions from all fields of science and from any source. The editors are committed to the prompt evaluation and publication of submitted papers while upholding high standards that support reproducibility of published research. Science is published weekly; selected papers are published online ahead of print.
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