TY - JOUR
T1 - Evolutionary adaptations of doublet microtubules in trypanosomatid parasites
AU - Doran, Matthew H.
AU - Niu, Qingwei
AU - Zeng, Jianwei
AU - Beneke, Tom
AU - Smith, James
AU - Ren, Peter
AU - Fochler, Sophia
AU - Coscia, Adrian
AU - Höög, Johanna L.
AU - Meleppattu, Shimi
AU - Lishko, Polina V.
AU - Wheeler, Richard J.
AU - Gluenz, Eva
AU - Zhang, Rui
AU - Brown, Alan
N1 - Cryo-EM data of L. tarentolae DMTs were collected at the Harvard Cryo-EM Center for Structural Biology at Harvard Medical School (HMS). Cryo-EM data of C. fasciculata axonemes were collected at the Pacific Northwest Center for Cryo-EM (PNCC). We thank M. de Farias (PNCC) for assistance with cryo-EM data collection, R. Tomaino (HMS) for mass spectrometry analysis of L. tarentolae samples, M. Naldrett and S. Alvarez (University of Nebraska–Lincoln) for mass spectrometry analysis of C. fasciculata samples, and K. Gull (University of Oxford) for sharing facilities that enabled the mutant screen.
PY - 2025/3/14
Y1 - 2025/3/14
N2 - 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, Leishmania tarentolae and Crithidia fasciculata, 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 behavior. Our study shows that proper B-tubule closure is critical for flagellar motility, exemplifying how integrating structural identification with systematic gene deletion can dissect individual protein contributions to flagellar motility.
AB - 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, Leishmania tarentolae and Crithidia fasciculata, 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 behavior. Our study shows that proper B-tubule closure is critical for flagellar motility, exemplifying how integrating structural identification with systematic gene deletion can dissect individual protein contributions to flagellar motility.
UR - https://www.ebi.ac.uk/emdb/
UR - https://doi.org/10.2210/pdb9e78/pdb
UR - https://www.ncbi.nlm.nih.gov/genbank/
UR - https://doi.org/10.48620/85573
U2 - 10.1126/science.adr5507
DO - 10.1126/science.adr5507
M3 - Article
SN - 0036-8075
JO - Science
JF - Science
M1 - eadr5507
ER -