Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
Binding of IFT22 to the intraflagellar transport complex is essential for flagellum assembly. / Wachter, Stefanie; Jung, Jamin; Shafiq, Shahaan; Basquin, Jerome; Fort, Cécile; Bastin, Philippe; Lorentzen, Esben.
In: EMBO Journal, Vol. 38, No. 9, e101251, 05.2019.Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
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TY - JOUR
T1 - Binding of IFT22 to the intraflagellar transport complex is essential for flagellum assembly
AU - Wachter, Stefanie
AU - Jung, Jamin
AU - Shafiq, Shahaan
AU - Basquin, Jerome
AU - Fort, Cécile
AU - Bastin, Philippe
AU - Lorentzen, Esben
PY - 2019/5
Y1 - 2019/5
N2 - 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.
AB - 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.
KW - cilia
KW - GTPase
KW - IFT22
KW - intraflagellar transport
KW - Trypanosoma brucei
UR - http://www.scopus.com/inward/record.url?scp=85063799499&partnerID=8YFLogxK
U2 - 10.15252/embj.2018101251
DO - 10.15252/embj.2018101251
M3 - Journal article
C2 - 30940671
AN - SCOPUS:85063799499
VL - 38
JO - E M B O Journal
JF - E M B O Journal
SN - 0261-4189
IS - 9
M1 - e101251
ER -