Structures of Native Doublet Microtubules from Trichomonas vaginalis Reveal Parasite-Specific Proteins
Year: 2025
Type: article
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.
Source: Nature Communications
Authors: Alexander Stevens, Saarang Kashyap, Ethan H. Crofut, Shuqi E. Wang, Katherine A. Muratore, Patricia J. Johnson, Z. Hong Zhou
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: National Science Foundation, U.S. Department of Health and Human Services, James B. Pendleton Charitable Trust, National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Division of Materials Research, National Center for Research Resources, UCLA AIDS Institute
Awards: G1395360581, G1535198665, G259219952, G3103422320, G3299242641, MRI: Acquisition of a direct electron detector for the UCLA Titan electron microscope, Inhibitors of Nitro Drug Targets as Antimicrobials against Trichomonas Vaginalis, Direct Detection Device for atomic resolution cryoEM of macromolecular complexes, High-End CryoEM Instrument for the UCLA Electron Imaging Center for Nanomachines, G7152664478, G7234115791, G7595416162, Science and Technology Center on Real-Time Functional Imaging (STROBE), G9000252771, G9000342382, Multidisciplinary Training in Microbial Pathogenesis
OpenAlex ID: W4409947646