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Peer-reviewedCC BY-NC-ND 4.0Proceedings of the National Academy of Sciences of the United States of America

Unveiling the structure of Leishmania flagella through cryoelectron tomography

  • Dylan Wilburn1
  • Justine Pinskey1
  • Hao Zhu1
  • Binita Nepal2,3
  • Nhan Phan1
  • Dawn M. Wetzel2,3
  • Daniela Nicastro1
  1. 1Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390
  2. 2Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX 75390
  3. 3Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390
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Abstract

Leishmania are unicellular parasites that cause the serious disease leishmaniasis, presenting ongoing global challenges as existing treatments face issues with resistance and toxicity. Leishmania contain a single motile flagellum, essential for transmission, which has the conserved [9 + 2] microtubule arrangement. We used cryoelectron tomography to determine the ultrastructure of the Leishmania tarentolae 96-nm repeat and paraflagellar rod. While the overall structure, including three broad radial spokes and two-headed outer dynein arms, resembles other eukaryotes like Trypanosoma brucei, Tetrahymena, and Opisthokonts, the Leishmania flagellum also exhibits unique and asymmetrical features. These include asymmetrically shaped radial spoke heads similar to T. brucei, suggesting this may represent a kinetoplastid-specific feature. Further, Leishmania contain an additional inner-junction and 8-nm wide A2 protofilament hole. Strikingly, Leishmania have many doublet-specific structures such as outer dynein arm tethers, interdoublet linkers, and heterogeneous connections to the paraflagellar rod. In this work, we show that divergent structural traits of Leishmania flagella highlight lineage-specific adaptations within eukaryotes.

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Cite

BibTeXRIS
BibTeX
@article{wilburn2026unveiling,
  title = {{Unveiling the structure of Leishmania flagella through cryoelectron tomography}},
  author = {Dylan Wilburn and Justine Pinskey and Hao Zhu and Binita Nepal and Nhan Phan and Dawn M. Wetzel and Daniela Nicastro},
  journal = {Proceedings of the National Academy of Sciences of the United States of America},
  year = {2026},
  month = oct,
  doi = {10.1073/pnas.2616874123},
  url = {https://doi.org/10.1073/pnas.2616874123},
  note = {CC BY-NC-ND 4.0},
}
RIS
TY  - JOUR
TI  - Unveiling the structure of Leishmania flagella through cryoelectron tomography
AU  - Dylan Wilburn
AU  - Justine Pinskey
AU  - Hao Zhu
AU  - Binita Nepal
AU  - Nhan Phan
AU  - Dawn M. Wetzel
AU  - Daniela Nicastro
PY  - 2026
DA  - 2026/10/21
JO  - Proceedings of the National Academy of Sciences of the United States of America
DO  - 10.1073/pnas.2616874123
UR  - https://doi.org/10.1073/pnas.2616874123
AB  - Leishmania are unicellular parasites that cause the serious disease leishmaniasis, presenting ongoing global challenges as existing treatments face issues with resistance and toxicity. Leishmania contain a single motile flagellum, essential for transmission, which has the conserved [9 + 2] microtubule arrangement. We used cryoelectron tomography to determine the ultrastructure of the Leishmania tarentolae 96-nm repeat and paraflagellar rod. While the overall structure, including three broad radial spokes and two-headed outer dynein arms, resembles other eukaryotes like Trypanosoma brucei, Tetrahymena, and Opisthokonts, the Leishmania flagellum also exhibits unique and asymmetrical features. These include asymmetrically shaped radial spoke heads similar to T. brucei, suggesting this may represent a kinetoplastid-specific feature. Further, Leishmania contain an additional inner-junction and 8-nm wide A2 protofilament hole. Strikingly, Leishmania have many doublet-specific structures such as outer dynein arm tethers, interdoublet linkers, and heterogeneous connections to the paraflagellar rod. In this work, we show that divergent structural traits of Leishmania flagella highlight lineage-specific adaptations within eukaryotes.
SN  - 0027-8424
SN  - 1091-6490
ER  -