# Structures of Native Doublet Microtubules from Trichomonas vaginalis Reveal Parasite-Specific Proteins as Potential Drug Targets

## TL;DR

This study reveals the structure of doublet microtubules in the parasite Trichomonas vaginalis, identifying unique proteins that could be targeted for drug development.

## Contribution

The first atomic model of native Trichomonas vaginalis doublet microtubules is presented, revealing parasite-specific proteins and a potential drug molecule.

## Key findings

- The cryo-EM structure of native Tv-DMTs identified 29 unique proteins, including 18 microtubule inner proteins and 9 outer proteins.
- Parasite-specific proteins like TvFAP40 and TvFAP35 stabilize DMTs and are essential for Tv locomotion.
- A small molecule, IP6, is found in a pocket of TvFAP40, suggesting potential for drug design.

## 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, such as 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 rational design of therapeutics.