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Täschner, M.* ; Lorentzen, A.* ; Mourao, A. ; Collins, T.* ; Freke, G.M.* ; Moulding, D.* ; Basquin, J.* ; Jenkins, D.* ; Lorentzen, E.*

Crystal structure of intraflagellar transport protein 80 reveals a homodimer required for ciliogenesis.

eLife 7:e33067 (2018)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
Oligomeric assemblies of intraflagellar transport (IFT) particles build cilia through sequential recruitment and transport of ciliary cargo proteins within cilia. Here we present the 1.8 Å resolution crystal structure of the Chlamydomonas IFT-B protein IFT80, which reveals the architecture of two N-terminal β-propellers followed by an α-helical extension. The N-terminal β-propeller tethers IFT80 to the IFT-B complex via IFT38 whereas the second β-propeller and the C-terminal αa-helical extension result in IFT80 homo-dimerization. Using CRISPR/Cas to create biallelic Ift80 frameshift mutations in IMCD3 mouse cells, we demonstrate that IFT80 is absolutely required for ciliogenesis. Structural mapping and rescue experiments reveal that human disease-causing missense mutations do not cluster within IFT80 and form functional IFT particles. Unlike missense mutant forms of IFT80, deletion of the C-terminal dimerization domain prevented rescue of ciliogenesis. Taken together our results may provide a first insight into higher order IFT complex formation likely required for IFT train formation.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Cell Biology ; Molecular Biophysics ; Mouse ; Structural Biology
ISSN (print) / ISBN 2050-084X
e-ISSN 2050-084X
Zeitschrift eLife
Quellenangaben Band: 7, Heft: , Seiten: , Artikelnummer: e33067 Supplement: ,
Verlag eLife Sciences Publications
Begutachtungsstatus Peer reviewed