EMD-28805
Subtomographic average of flagellar axoneme doublet from Trypanosoma brucei Wildtype Control 2
EMD-28805
Subtomogram averaging24.0 Å
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Map released: 06/09/2023
Last modified: 06/09/2023
Sample Organism:
Trypanosoma brucei
Sample: Detergent-extracted flagellum of Trypanosoma brucei
Deposition Authors: Shimogawa MM
,
Wang H
Sample: Detergent-extracted flagellum of Trypanosoma brucei
Deposition Authors: Shimogawa MM
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FAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction.
Shimogawa MM
,
Wijono AS,
Wang H
,
Zhang J
,
Sha J,
Szombathy N,
Vadakkan S,
Pelayo P,
Jonnalagadda K
,
Wohlschlegel J,
Zhou ZH
,
Hill KL
(2023) Nat Commun , 14 , 5225 - 5225
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(2023) Nat Commun , 14 , 5225 - 5225
Abstract:
Motility of pathogenic protozoa depends on flagella (synonymous with cilia) with axonemes containing nine doublet microtubules (DMTs) and two singlet microtubules. Microtubule inner proteins (MIPs) within DMTs influence axoneme stability and motility and provide lineage-specific adaptations, but individual MIP functions and assembly mechanisms are mostly unknown. Here, we show in the sleeping sickness parasite Trypanosoma brucei, that FAP106, a conserved MIP at the DMT inner junction, is required for trypanosome motility and functions as a critical interaction hub, directing assembly of several conserved and lineage-specific MIPs. We use comparative cryogenic electron tomography (cryoET) and quantitative proteomics to identify MIP candidates. Using RNAi knockdown together with fitting of AlphaFold models into cryoET maps, we demonstrate that one of these candidates, MC8, is a trypanosome-specific MIP required for parasite motility. Our work advances understanding of MIP assembly mechanisms and identifies lineage-specific motility proteins that are attractive targets to consider for therapeutic intervention.
Motility of pathogenic protozoa depends on flagella (synonymous with cilia) with axonemes containing nine doublet microtubules (DMTs) and two singlet microtubules. Microtubule inner proteins (MIPs) within DMTs influence axoneme stability and motility and provide lineage-specific adaptations, but individual MIP functions and assembly mechanisms are mostly unknown. Here, we show in the sleeping sickness parasite Trypanosoma brucei, that FAP106, a conserved MIP at the DMT inner junction, is required for trypanosome motility and functions as a critical interaction hub, directing assembly of several conserved and lineage-specific MIPs. We use comparative cryogenic electron tomography (cryoET) and quantitative proteomics to identify MIP candidates. Using RNAi knockdown together with fitting of AlphaFold models into cryoET maps, we demonstrate that one of these candidates, MC8, is a trypanosome-specific MIP required for parasite motility. Our work advances understanding of MIP assembly mechanisms and identifies lineage-specific motility proteins that are attractive targets to consider for therapeutic intervention.