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EMBO J. 2019 Apr 2. pii: e101251. doi: 10.15252/embj.2018101251. [Epub ahead of print]

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

Author information

1
Department of Structural Cell Biology, Max Planck Institute of Biochemistry, Martinsried, Germany.
2
Trypanosome Cell Biology Unit, Institut Pasteur & INSERM U1201, Paris, France.
3
Department of Molecular Biology and Genetics, Aarhus University, Aarhus C, Denmark el@mbg.au.dk.

Abstract

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.

KEYWORDS:

Trypanosoma brucei ; GTPase; IFT22; cilia; intraflagellar transport

PMID:
30940671
DOI:
10.15252/embj.2018101251

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