Trypanosome doublet microtubule structures reveal flagellum assembly and motility mechanisms

• 成果类型: Article
• 署名作者: Xia, Xian; Shimogawa, Michelle M.; Wang, Hui; Liu, Samuel; Wijono, Angeline; Langousis, Gerasimos; Kassem, Ahmad M.; Wohlschlegel, James A.; Hill, Kent L.; Zhou, Z. Hong
• 署名单位: University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles; University of California System; University of California Los Angeles
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11370
• DOI: 10.1126/science.adr3314
• 发表日期: 2025-03-14
• 关键词: inducible expression system; conserved axonemal protein; dynein regulatory complex; cryo-em; african trypanosomes; adenylate cyclases; paraflagellar rod; crystal-structure; brucei; components

摘要

The flagellum of Trypanosoma brucei drives the parasite's characteristic screw-like motion and is essential for its replication, transmission, and pathogenesis. However, the molecular details of this process remain unclear. Here, we present high-resolution (up to 2.8 angstrom) cryo-electron microscopy structures of T. brucei flagellar doublet microtubules (DMTs). Integrated modeling identified 154 different axonemal proteins inside and outside the DMT and, together with genetic and proteomic interrogation, revealed conserved and trypanosome-specific foundations of flagellum assembly and motility. We captured axonemal dynein motors in their pre-power stroke state. Comparing atomic models between pre- and post-power strokes defined how dynein structural changes drive sliding of adjacent DMTs during flagellar beating. This study illuminates structural dynamics underlying flagellar motility and identifies pathogen-specific proteins to consider for therapeutic interventions targeting neglected diseases.