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Structure paper

TitleTrypanosome doublet microtubule structures reveal flagellum assembly and motility mechanisms.
Journal, issue, pagesScience, Vol. 387, Issue 6739, Page eadr3314, Year 2025
Publish dateMar 14, 2025
AuthorsXian Xia / Michelle M Shimogawa / Hui Wang / Samuel Liu / Angeline Wijono / Gerasimos Langousis / Ahmad M Kassem / James A Wohlschlegel / Kent L Hill / Z Hong Zhou /
PubMed AbstractThe flagellum of 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 ...The flagellum of 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 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.
External linksScience / PubMed:40080582
MethodsEM (single particle)
Resolution2.8 - 7.6 Å
Structure data

EMDB-47409: Structure of 48-nm repeat DMT from Trypanosoma brucei FAP106A-KD
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-47410: Cryo-EM structure of 48-nm repeat of DMT from Trypanosoma brucei FAP106B-KD
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-47411: Cryo-EM structure of 48-nm repeat of DMT from Trypanosoma brucei PBP36-KD
Method: EM (single particle) / Resolution: 3.5 Å

47451

9e2g

EMDB-47451, PDB-9e2g:
Cryo-EM structure of 48 nm repeat of microtubule doublet from T. brucei flagellum
Method: EM (single particle) / Resolution: 2.8 Å

47524

9e5c

EMDB-47524, PDB-9e5c:
Cryo-EM structure of 96 nm repeat of microtubule doublet from T. brucei flagellum
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-47559: Focus refine map of T. brucei DMT 48 nm repeat part1-1
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-47560: Focus refine map of T. brucei DMT 48 nm repeat part1-2
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-47561: Focus refine map of T. brucei DMT 48 nm repeat part1-3
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-47562: Focus refine map of T. brucei DMT 48 nm repeat part1-4
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-47563: Focus refine map of T. brucei DMT 48 nm repeat part1-5
Method: EM (single particle) / Resolution: 2.8 Å

EMDB-47567: Focus refine map of T. brucei DMT 48 nm repeat part1-6
Method: EM (single particle) / Resolution: 3.4 Å

EMDB-47568: Focus refine map of T. brucei DMT 48 nm repeat part1-7
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-47569: Focus refine map of T. brucei DMT 48 nm repeat part2-1
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-47574: Focus refine map of T. brucei DMT 48 nm repeat part2-2
Method: EM (single particle) / Resolution: 3.1 Å

EMDB-47575: Focus refine map of T. brucei DMT 48 nm repeat part2-3
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-47579: Focus refine map of T. brucei DMT 48 nm repeat part2-5
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-47581: Focus refine map of T. brucei DMT 48 nm repeat part2-6
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-47582: Focus refine map of T. brucei DMT 48 nm repeat part2-7
Method: EM (single particle) / Resolution: 3.3 Å

EMDB-47590: Overall map of T. brucei DMT 48 nm repeat
Method: EM (single particle) / Resolution: 3.2 Å

EMDB-47591: Focus refine map of T. brucei DMT 96 nm repeat DMT part1
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-47593: Focus refine map of T. brucei DMT 96 nm repeat DMT part2
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-47594: Focus refine map of T. brucei DMT 96 nm repeat radial spoke 1 stalk
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-47595: Focus refine map of T. brucei DMT 96 nm repeat DMT part3
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-47596: Focus refine map of T. brucei DMT 96 nm repeat IDA-a base
Method: EM (single particle) / Resolution: 3.8 Å

EMDB-47597: Focus refine map of T. brucei DMT 96 nm repeat IDA-b base
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-47598: Focus refine map of T. brucei DMT 96 nm repeat radial spoke 2 stalk
Method: EM (single particle) / Resolution: 4.1 Å

EMDB-47599: Focus refine map of T. brucei DMT 96 nm repeat N-DRC base
Method: EM (single particle) / Resolution: 3.6 Å

EMDB-47602: Focus refine map of T. brucei DMT 96 nm repeat radial spoke 3 base
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-47603: Focus refine map of T. brucei DMT 96 nm repeat radial spoke 3 MOP84
Method: EM (single particle) / Resolution: 3.5 Å

EMDB-47621: Focus refine map of T. brucei DMT 96 nm repeat radial spoke 1 head region lobe1
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-47623: Focus refine map of T. brucei DMT 96 nm repeat radial spoke 1 head region lobe2
Method: EM (single particle) / Resolution: 6.4 Å

EMDB-47625: Focus refine map of T. brucei DMT 96 nm repeat radial spoke 2 head region lobe1
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-47626: Focus refine map of T. brucei DMT 96 nm repeat radial spoke 2 head region lobe2
Method: EM (single particle) / Resolution: 6.9 Å

EMDB-47629: Focus refine map of T. brucei DMT 96 nm repeat ODA IC-LC region
Method: EM (single particle) / Resolution: 4.5 Å

EMDB-47631: Focus refine map of T. brucei DMT 96 nm repeat ODA-beta motor domain
Method: EM (single particle) / Resolution: 3.9 Å

EMDB-47632: Focus refine map of T. brucei DMT 96 nm repeat ODA-alpha motor domain
Method: EM (single particle) / Resolution: 3.7 Å

EMDB-47634: Focus refine map of T. brucei DMT 96 nm repeat IDAf IC-LC region
Method: EM (single particle) / Resolution: 7.6 Å

EMDB-47637: Focus refine map of T. brucei DMT 96 nm repeat IDAf head region
Method: EM (single particle) / Resolution: 7.2 Å

EMDB-47652: Focus refine map of T. brucei DMT 96 nm repeat IDA-a
Method: EM (single particle) / Resolution: 7.6 Å

EMDB-47653: Focus refine map of T. brucei DMT 96 nm repeat IDA-b
Method: EM (single particle) / Resolution: 7.6 Å

EMDB-47654: Focus refine map of T. brucei DMT 96 nm repeat N-DRC distal region
Method: EM (single particle) / Resolution: 4.4 Å

EMDB-47656: overall map of T. brucei DMT 96 nm repeat
Method: EM (single particle) / Resolution: 4.1 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-GDP:
GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying molecule*YM

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

Source
  • trypanosoma brucei brucei treu927 (eukaryote)
KeywordsMOTOR PROTEIN / flagella / microtubule

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