Evolutionary adaptations of doublet microtubules in trypanosomatid parasites

IF 44.7 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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Science 综合性期刊-综合性期刊

CiteScore

61.10

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0.90%

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审稿时长

2.1 months

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