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TitleFAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 5225, Year 2023
Publish dateAug 26, 2023
AuthorsMichelle M Shimogawa / Angeline S Wijono / Hui Wang / Jiayan Zhang / Jihui Sha / Natasha Szombathy / Sabeeca Vadakkan / Paula Pelayo / Keya Jonnalagadda / James Wohlschlegel / Z Hong Zhou / Kent L Hill /
PubMed AbstractMotility of pathogenic protozoa depends on flagella (synonymous with cilia) with axonemes containing nine doublet microtubules (DMTs) and two singlet microtubules. Microtubule inner proteins (MIPs) ...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.
External linksNat Commun / PubMed:37633952 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution16.5 - 24.0 Å
Structure data

EMDB-28802: Subtomographic average of flagellar axoneme doublet from Trypanosoma brucei FAP106 knockdown mutant
Method: EM (subtomogram averaging) / Resolution: 19.5 Å

EMDB-28803: Subtomographic average of flagellar axoneme doublet from Trypanosoma brucei Wildtype
Method: EM (subtomogram averaging) / Resolution: 18.5 Å

EMDB-28804: Subtomographic average of flagellar axoneme doublet from Trypanosoma brucei MC8 Knockdown mutant
Method: EM (subtomogram averaging) / Resolution: 16.5 Å

EMDB-28805: Subtomographic average of flagellar axoneme doublet from Trypanosoma brucei Wildtype Control 2
Method: EM (subtomogram averaging) / Resolution: 24.0 Å

Source
  • Trypanosoma brucei (eukaryote)

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