The molecular structure of IFT-A and IFT-B in anterograde intraflagellar transport trains.

Autor: Lacey SE; Human Technopole, Milan, Italy., Foster HE; Human Technopole, Milan, Italy., Pigino G; Human Technopole, Milan, Italy. gaia.pigino@fht.org.
Jazyk: angličtina
Zdroj: Nature structural & molecular biology [Nat Struct Mol Biol] 2023 May; Vol. 30 (5), pp. 584-593. Date of Electronic Publication: 2023 Jan 02.
DOI: 10.1038/s41594-022-00905-5
Abstrakt: Anterograde intraflagellar transport (IFT) trains are essential for cilia assembly and maintenance. These trains are formed of 22 IFT-A and IFT-B proteins that link structural and signaling cargos to microtubule motors for import into cilia. It remains unknown how the IFT-A/-B proteins are arranged into complexes and how these complexes polymerize into functional trains. Here we use in situ cryo-electron tomography of Chlamydomonas reinhardtii cilia and AlphaFold2 protein structure predictions to generate a molecular model of the entire anterograde train. We show how the conformations of both IFT-A and IFT-B are dependent on lateral interactions with neighboring repeats, suggesting that polymerization is required to cooperatively stabilize the complexes. Following three-dimensional classification, we reveal how IFT-B extends two flexible tethers to maintain a connection with IFT-A that can withstand the mechanical stresses present in actively beating cilia. Overall, our findings provide a framework for understanding the fundamental processes that govern cilia assembly.
(© 2023. The Author(s).)
Databáze: MEDLINE
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