biostudies-literatureDoran MHNIAID NIH HHSWellcome TrustNIGMS NIH HHSeadr5507https://www.ebi.ac.uk/biostudies/studies/S-EPMC7617938biostudies-literatureUnknown387(6739)The movement and pathogenicity of trypanosomatid species, the causative agents of trypanosomiasis and leishmaniasis, are dependent on a flagellum that contains an axoneme of dynein-bound doublet microtubules (DMTs). In this work, we present cryo-electron microscopy structures of DMTs from two trypanosomatid species, <i>Leishmania tarentolae</i> and <i>Crithidia fasciculata</i>, at resolutions up to 2.7 angstrom. The structures revealed 27 trypanosomatid-specific microtubule inner proteins, a specialized dynein-docking complex, and the presence of paralogous proteins that enable higher-order periodicities or proximal-distal patterning. Leveraging the genetic tractability of trypanosomatid species, we quantified the location and contribution of each structure-identified protein to swimming bScience (New York, N.Y.)Evolutionary adaptations of doublet microtubules in trypanosomatid parasites.PMC7617938R01 AI179885211075/Z/18/ZR01 GM143183R01 GM141109R01 GM138854Brown AFochler SWheeler RJZhang RSmith JBeneke TCoscia ADoran MHHoog JLNiu QLishko PVZeng JRen PGluenz EMeleppattu SfalseEvolutionary adaptations of doublet microtubules in trypanosomatid parasites.The movement and pathogenicity of trypanosomatid species, the causative agents of trypanosomiasis and leishmaniasis, are dependent on a flagellum that contains an axoneme of dynein-bound doublet microtubules (DMTs). In this work, we present cryo-electron microscopy structures of DMTs from two trypanosomatid species, <i>Leishmania tarentolae</i> and <i>Crithidia fasciculata</i>, at resolutions up to 2.7 angstrom. The structures revealed 27 trypanosomatid-specific microtubule inner proteins, a specialized dynein-docking complex, and the presence of paralogous proteins that enable higher-order periodicities or proximal-distal patterning. Leveraging the genetic tractability of trypanosomatid species, we quantified the location and contribution of each structure-identified protein to swimming b2025-01-01T00:00:00Z2025 Mar2026-03-16T08:59:04.211Z2025-08-17T03:06:13.482ZS-EPMC76179384008057710.1126/science.adr5507