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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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