Evolutionary adaptations of doublet microtubules in trypanosomatid parasites

• 成果类型: Article
• 署名作者: Doran, Matthew H.; Niu, Qingwei; Zeng, Jianwei; Beneke, Tom; Smith, James; Ren, Peter; Fochler, Sophia; Coscia, Adrian; Hoeoeg, Johanna L.; Meleppattu, Shimi; Lishko, Polina V.; Wheeler, Richard J.; Gluenz, Eva; Zhang, Rui; Brown, Alan
• 署名单位: Harvard University; Harvard Medical School; Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); University of Oxford; University of Bern; University of Gothenburg; University of Oxford; University of Edinburgh; University of Wurzburg; Harry Perkins Institute of Medical Research
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13193
• DOI: 10.1126/science.adr5507
• 发表日期: 2025-03-14
• 关键词: cryo-em; protein; flagellum; refinement; motility; reveals; dna

摘要

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.