National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM138854
米国
National Institutes of Health/National Institute Of Allergy and Infectious Diseases (NIH/NIAID)
R01AI179885
米国
引用
ジャーナル: Science / 年: 2025 タイトル: Evolutionary adaptations of doublet microtubules in trypanosomatid parasites. 著者: 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 ...著者: 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 / 要旨: 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 ...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, and , 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.