Structures of Native Doublet Microtubules from Trichomonas Vaginalis Reveal Parasite-Specific Proteins as Potential Drug Targets. Stevens, A., Kashyap, S., Crofut, E. H., Wang, S. E., Muratore, K. A., Johnson, P. J., & Zhou, Z. H. June, 2024. doi abstract bibtex 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 DMT structures has prevented structure-guided drug design to manage Tv infection. Here, we determined the cryo-EM structure of native Tv-DMTs, identifying 29 unique proteins, including 18 microtubule inner proteins and 9 microtubule outer proteins. While the A-tubule is simplistic compared to DMTs of other organisms, the B-tubule features specialized, parasite-specific proteins, like TvFAP40 and TvFAP35 that form filaments near the inner and outer junctions, respectively, to stabilize DMTs and enable Tv locomotion. Notably, a small molecule, assigned as IP6, is coordinated within a pocket of TvFAP40 and has characteristics of a drug molecule. This first atomic model of the Tv-DMT highlights the diversity of eukaryotic motility machinery and provides a structural framework to inform the rational design of therapeutics.
@misc{stevensStructuresNativeDoublet2024,
title = {Structures of {{Native Doublet Microtubules}} from {{Trichomonas}} Vaginalis {{Reveal Parasite-Specific Proteins}} as {{Potential Drug Targets}}},
author = {Stevens, Alexander and Kashyap, Saarang and Crofut, Ethan H. and Wang, Shuqi E. and Muratore, Katherine A. and Johnson, Patricia J. and Zhou, Z. Hong},
year = {2024},
month = jun,
primaryclass = {New Results},
pages = {2024.06.11.598142},
publisher = {bioRxiv},
doi = {10.1101/2024.06.11.598142},
urldate = {2025-04-04},
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 DMT structures has prevented structure-guided drug design to manage Tv infection. Here, we determined the cryo-EM structure of native Tv-DMTs, identifying 29 unique proteins, including 18 microtubule inner proteins and 9 microtubule outer proteins. While the A-tubule is simplistic compared to DMTs of other organisms, the B-tubule features specialized, parasite-specific proteins, like TvFAP40 and TvFAP35 that form filaments near the inner and outer junctions, respectively, to stabilize DMTs and enable Tv locomotion. Notably, a small molecule, assigned as IP6, is coordinated within a pocket of TvFAP40 and has characteristics of a drug molecule. This first atomic model of the Tv-DMT highlights the diversity of eukaryotic motility machinery and provides a structural framework to inform the rational design of therapeutics.},
archiveprefix = {bioRxiv},
chapter = {New Results},
copyright = {{\copyright} 2024, Posted by Cold Spring Harbor Laboratory. The copyright holder for this pre-print is the author. All rights reserved. The material may not be redistributed, re-used or adapted without the author's permission.},
langid = {english},
file = {C:\Users\shervinnia\Zotero\storage\H9LYDR3F\Stevens et al. - 2024 - Structures of Native Doublet Microtubules from Trichomonas vaginalis Reveal Parasite-Specific Protei.pdf}
}
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