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Crystal structures of IFT70/52 and IFT52/46 provide insight into intraflagellar transport B core complex assembly

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Taschner,  Michael
Lorentzen, Esben / Intraflagellar Transport, Max Planck Institute of Biochemistry, Max Planck Society;

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Braeuer,  Philipp
Lorentzen, Esben / Intraflagellar Transport, Max Planck Institute of Biochemistry, Max Planck Society;

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Lorentzen,  Esben
Lorentzen, Esben / Intraflagellar Transport, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

Taschner, M., Kotsis, F., Braeuer, P., Kuehn, E. W., & Lorentzen, E. (2014). Crystal structures of IFT70/52 and IFT52/46 provide insight into intraflagellar transport B core complex assembly. JOURNAL OF CELL BIOLOGY, 207(2), 269-282. doi:10.1083/jcb.201408002.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0024-5B05-F
Abstract
Cilia are microtubule-based organelles that assemble via intraflagellar transport (IFT) and function as signaling hubs on eukaryotic cells. IFT relies on molecular motors and IFT complexes that mediate the contacts with ciliary cargo. To elucidate the architecture of the IFT-B complex, we reconstituted and purified the nonameric IFT-B core from Chlamydomonas reinhardtii and determined the crystal structures of C. reinhardtii IFT70/52 and Tetrahymena IFT52/46 subcomplexes. The 2.5-angstrom resolution IFT70/52 structure shows that IFT52(330-370) is buried deeply within the IFT70 tetratricopeptide repeat superhelix. Furthermore, the polycystic kidney disease protein IFT88 binds IFT52(281-329) in a complex that interacts directly with IFT70/IFT52(330-381) in trans. The structure of IFT52C/IFT46C was solved at 2.3 angstrom resolution, and we show that it is essential for IFT-B core integrity by mediating interaction between IFT88/70/52/46 and IFT81/74/27/25/22 subcomplexes. Consistent with this, overexpression of mammalian IFT52C in MDCK cells is dominant-negative and causes IFT protein mislocalization and disrupted ciliogenesis. These data further rationalize several ciliogenesis phenotypes of IFT mutant strains.