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

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Documents

DOI

  • Michael Taschner
  • ,
  • Anna Lorentzen
  • André Mourão, Helmholtz Zentrum München - German Research Center for Environmental Health
  • ,
  • Toby Collins, UCL
  • ,
  • Grace M. Freke, UCL
  • ,
  • Dale Moulding, UCL Institute of Child Health, London, UK.
  • ,
  • Jerome Basquin, Max Planck Institute of Biochemistry
  • ,
  • Dagan Jenkins, UCL
  • ,
  • Esben Lorentzen

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

See relations at Aarhus University Citationformats

Download statistics

No data available

ID: 131008975