Binding of IFT22 to the intraflagellar transport complex is essential for flagellum assembly

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Stefanie Wachter, Max Planck Institute of Biochemistry
  • ,
  • Jamin Jung, Institut Pasteur, Paris
  • ,
  • Shahaan Shafiq, Institut Pasteur, Paris
  • ,
  • Jerome Basquin, Max Planck Institute of Biochemistry
  • ,
  • Cécile Fort, Institut Pasteur, Paris
  • ,
  • Philippe Bastin, Institut Pasteur, Paris
  • ,
  • Esben Lorentzen

Intraflagellar transport (IFT) relies on motor proteins and the IFT complex to construct cilia and flagella. The IFT complex subunit IFT22/RabL5 has sequence similarity with small GTPases although the nucleotide specificity is unclear because of non-conserved G4/G5 motifs. We show that IFT22 specifically associates with G-nucleotides and present crystal structures of IFT22 in complex with GDP, GTP, and with IFT74/81. Our structural analysis unravels an unusual GTP/GDP-binding mode of IFT22 bypassing the classical G4 motif. The GTPase switch regions of IFT22 become ordered upon complex formation with IFT74/81 and mediate most of the IFT22-74/81 interactions. Structure-based mutagenesis reveals that association of IFT22 with the IFT complex is essential for flagellum construction in Trypanosoma brucei although IFT22 GTP-loading is not strictly required.

Original languageEnglish
Article numbere101251
JournalEMBO Journal
Volume38
Issue9
ISSN0261-4189
DOIs
Publication statusPublished - May 2019

    Research areas

  • cilia, GTPase, IFT22, intraflagellar transport, Trypanosoma brucei

See relations at Aarhus University Citationformats

ID: 152351044