An amino acid-resolution interactome for motile cilia identifies the structure and function of ciliopathy protein complexes.

Autor:	McCafferty CL; Department of Molecular Biosciences, University of Texas, Austin, Austin, TX 78712, USA; Biozentrum, University of Basel, 4056 Basel, Switzerland. Electronic address: caitie.mccafferty@gmail.com., Papoulas O; Department of Molecular Biosciences, University of Texas, Austin, Austin, TX 78712, USA., Lee C; Department of Molecular Biosciences, University of Texas, Austin, Austin, TX 78712, USA., Bui KH; Department of Anatomy and Cell Biology, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC, Canada., Taylor DW; Department of Molecular Biosciences, University of Texas, Austin, Austin, TX 78712, USA., Marcotte EM; Department of Molecular Biosciences, University of Texas, Austin, Austin, TX 78712, USA. Electronic address: marcotte@utexas.edu., Wallingford JB; Department of Molecular Biosciences, University of Texas, Austin, Austin, TX 78712, USA. Electronic address: wallingford@austin.utexas.edu.
Jazyk:	angličtina
Zdroj:	Developmental cell [Dev Cell] 2024 Dec 12. Date of Electronic Publication: 2024 Dec 12.
DOI:	10.1016/j.devcel.2024.11.019
Abstrakt:	Motile cilia are ancient, evolutionarily conserved organelles whose dysfunction underlies motile ciliopathies, a broad class of human diseases. Motile cilia contain a myriad of different proteins that assemble into an array of distinct machines, and understanding the interactions and functional hierarchies among them presents an important challenge. Here, we defined the protein interactome of motile axonemes using cross-linking mass spectrometry in Tetrahymena thermophila. From over 19,000 cross-links, we identified over 4,700 unique amino acid interactions among over 1,100 distinct proteins, providing both macromolecular and atomic-scale insights into diverse ciliary machines, including the intraflagellar transport system, axonemal dynein arms, radial spokes, the 96-nm ruler, and microtubule inner proteins. Guided by this dataset, we used vertebrate multiciliated cells to reveal functional interactions among several poorly defined human ciliopathy proteins. This dataset provides a resource for studying the biology of an ancient organelle and the molecular etiology of human genetic disease. Competing Interests: Declaration of interests J.B.W. is a member of the advisory board of Developmental Cell, which had no input in the conduct of this research. E.M.M. is a co-founder, shareholder, and scientific advisory board member of Erisyon, Inc., which played no role in this work. (Copyright © 2024 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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