Trypanosome doublet microtubule structures reveal flagellum assembly and motility mechanisms
Xian Xia, Michelle M. Shimogawa, Hui Wang, Samuel Liu, Angeline S. Wijono, Gerasimos Langousis, Ahmad Kassem, James A. Wohlschlegel, Kent L. Hill, Z. Hong Zhou
Abstract
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.