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Structures of Native Doublet Microtubules from Trichomonas vaginalis Reveal Parasite-Specific Proteins

Author

Listed:
  • Alexander Stevens

    (University of California, Los Angeles (UCLA)
    UCLA
    UCLA)

  • Saarang Kashyap

    (University of California, Los Angeles (UCLA)
    UCLA)

  • Ethan H. Crofut

    (University of California, Los Angeles (UCLA)
    UCLA)

  • Shuqi E. Wang

    (University of California, Los Angeles (UCLA))

  • Katherine A. Muratore

    (University of California, Los Angeles (UCLA))

  • Patricia J. Johnson

    (University of California, Los Angeles (UCLA))

  • Z. Hong Zhou

    (University of California, Los Angeles (UCLA)
    UCLA
    UCLA)

Abstract

Doublet microtubules (DMTs) are flagellar components required for the protist Trichomonas vaginalis (Tv) to swim through the human genitourinary tract to cause trichomoniasis, the most common non-viral sexually transmitted disease. Lack of structures of Tv’s DMT (Tv-DMT) has prevented structure-guided drug design to manage Tv infection. Here, we determine the 16 nm, 32 nm, 48 nm and 96 nm-repeat structures of native Tv-DMT at resolution ranging from 3.4 to 4.4 Å by cryogenic electron microscopy (cryoEM) and built an atomic model for the entire Tv-DMT. These structures show that Tv-DMT is composed of 30 different proteins, including the α- and β-tubulin, 19 microtubule inner proteins (MIPs) and 9 microtubule outer proteins. While the A-tubule of Tv-DMT is simplistic compared to DMTs of other organisms, the B-tubule of Tv-DMT features parasite-specific proteins, such as TvFAP40 and TvFAP35. Notably, TvFAP40 and TvFAP35 form filaments near the inner and outer junctions, respectively, and interface with stabilizing MIPs. This atomic model of the Tv-DMT highlights diversity of eukaryotic motility machineries and provides a structural framework to inform rational design of therapeutics against trichomoniasis.

Suggested Citation

  • Alexander Stevens & Saarang Kashyap & Ethan H. Crofut & Shuqi E. Wang & Katherine A. Muratore & Patricia J. Johnson & Z. Hong Zhou, 2025. "Structures of Native Doublet Microtubules from Trichomonas vaginalis Reveal Parasite-Specific Proteins," Nature Communications, Nature, vol. 16(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59369-y
    DOI: 10.1038/s41467-025-59369-y
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    1. Kathryn Tunyasuvunakool & Jonas Adler & Zachary Wu & Tim Green & Michal Zielinski & Augustin Žídek & Alex Bridgland & Andrew Cowie & Clemens Meyer & Agata Laydon & Sameer Velankar & Gerard J. Kleywegt, 2021. "Highly accurate protein structure prediction for the human proteome," Nature, Nature, vol. 596(7873), pages 590-596, August.
    2. Robert A. Dick & Kaneil K. Zadrozny & Chaoyi Xu & Florian K. M. Schur & Terri D. Lyddon & Clifton L. Ricana & Jonathan M. Wagner & Juan R. Perilla & Barbie K. Ganser-Pornillos & Marc C. Johnson & Owen, 2018. "Inositol phosphates are assembly co-factors for HIV-1," Nature, Nature, vol. 560(7719), pages 509-512, August.
    3. Kiarash Jamali & Lukas Käll & Rui Zhang & Alan Brown & Dari Kimanius & Sjors H. W. Scheres, 2024. "Automated model building and protein identification in cryo-EM maps," Nature, Nature, vol. 628(8007), pages 450-457, April.
    4. John Jumper & Richard Evans & Alexander Pritzel & Tim Green & Michael Figurnov & Olaf Ronneberger & Kathryn Tunyasuvunakool & Russ Bates & Augustin Žídek & Anna Potapenko & Alex Bridgland & Clemens Me, 2021. "Highly accurate protein structure prediction with AlphaFold," Nature, Nature, vol. 596(7873), pages 583-589, August.
    5. Robert A. Dick & Kaneil K. Zadrozny & Chaoyi Xu & Florian K. M. Schur & Terri D. Lyddon & Clifton L. Ricana & Jonathan M. Wagner & Juan R. Perilla & Barbie K. Ganser-Pornillos & Marc C. Johnson & Owen, 2018. "Author Correction: Inositol phosphates are assembly co-factors for HIV-1," Nature, Nature, vol. 563(7731), pages 22-22, November.
    6. Shintaroh Kubo & Corbin S. Black & Ewa Joachimiak & Shun Kai Yang & Thibault Legal & Katya Peri & Ahmad Abdelzaher Zaki Khalifa & Avrin Ghanaeian & Caitlyn L. McCafferty & Melissa Valente-Paterno & Ch, 2023. "Native doublet microtubules from Tetrahymena thermophila reveal the importance of outer junction proteins," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    7. Michelle M. Shimogawa & Angeline S. Wijono & Hui Wang & Jiayan Zhang & Jihui Sha & Natasha Szombathy & Sabeeca Vadakkan & Paula Pelayo & Keya Jonnalagadda & James Wohlschlegel & Z. Hong Zhou & Kent L., 2023. "FAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    8. Jens S. Andersen & Aaran Vijayakumaran & Christopher Godbehere & Esben Lorentzen & Vito Mennella & Kenneth Bødtker Schou, 2024. "Uncovering structural themes across cilia microtubule inner proteins with implications for human cilia function," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    9. Vladimir A Fedorov & Philipp S Orekhov & Ekaterina G Kholina & Artem A Zhmurov & Fazoil I Ataullakhanov & Ilya B Kovalenko & Nikita B Gudimchuk, 2019. "Mechanical properties of tubulin intra- and inter-dimer interfaces and their implications for microtubule dynamic instability," PLOS Computational Biology, Public Library of Science, vol. 15(8), pages 1-25, August.
    10. Mikito Owa & Takayuki Uchihashi & Haru-aki Yanagisawa & Takashi Yamano & Hiro Iguchi & Hideya Fukuzawa & Ken-ichi Wakabayashi & Toshio Ando & Masahide Kikkawa, 2019. "Inner lumen proteins stabilize doublet microtubules in cilia and flagella," Nature Communications, Nature, vol. 10(1), pages 1-10, December.
    11. Travis Walton & Hao Wu & Alan Brown, 2021. "Structure of a microtubule-bound axonemal dynein," Nature Communications, Nature, vol. 12(1), pages 1-9, December.
    12. Travis Walton & Miao Gui & Simona Velkova & Mahmoud R. Fassad & Robert A. Hirst & Eric Haarman & Christopher O’Callaghan & Mathieu Bottier & Thomas Burgoyne & Hannah M. Mitchison & Alan Brown, 2023. "Axonemal structures reveal mechanoregulatory and disease mechanisms," Nature, Nature, vol. 618(7965), pages 625-633, June.
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