Crystal structure of intraflagellar transport protein 80 reveals a homo-dimer required for ciliogenesis

Michael Taschner, Anna Lorentzen, André Mourão, Toby Collins, Grace M. Freke, Dale Moulding, Jerome Basquin, Dagan Jenkins, Esben Lorentzen*

*Corresponding author for this work

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    Abstract

    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.

    Original languageEnglish
    Article numbere33067
    JournaleLife
    Volume7
    Number of pages27
    ISSN2050-084X
    DOIs
    Publication statusPublished - 16 Apr 2018

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