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Schlagwörter:
B CORE COMPLEX; TRYPANOSOMA-BRUCEI; CYTOPLASMIC DYNEIN; STRUCTURAL
BASIS; PROTEIN; GTPASE; MOUSE; PARTICLES; MOTILITY; HOMOLOGBiochemistry & Molecular Biology; Cell Biology; cilia; GTPase; IFT22; intraflagellar transport; Trypanosoma brucei;
Zusammenfassung:
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.
