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• W4383821461 abstract "Abstract Motile cilia are ancient, evolutionarily conserved organelles whose dysfunction underlies motile ciliopathies, a broad class of human diseases. Motile cilia contain myriad different proteins that assemble into an array of distinct machines, so 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 (XL/MS) in Tetrahymena thermophila . From over 19,000 XLs, we identified 4,757 unique amino acid interactions among 1,143 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, among others. Guided by this dataset, we used vertebrate multiciliated cells to reveal novel functional interactions among several poorly-defined human ciliopathy proteins. The dataset therefore provides a powerful resource for studying the basic biology of an ancient organelle and the molecular etiology of human genetic disease. Highlights Over 4,700 distinct amino-acid cross-links reveal the composition, structural organization, and conformational dynamics of proteins in motile ciliary axonemes. Dense interaction networks are defined for tubulins, Intraflagellar Transport complexes, axonemal dyneins, radial spokes, the CCDC39/40 96nm molecular ruler, and other complexes. These data reveal the placement of multiple adenylate kinases in the central apparatus and radial spokes of motile axonemes, a new microtubule-associated protein complex of CFAP58 and CCDC146, and insights into the activity of ciliopathy protein MAATS1/CFAP91. The data also provide the first known molecular defect resulting from loss of the human ciliopathy protein ENKUR." @default.
• W4383821461 created "2023-07-11" @default.
• W4383821461 creator A5029542971 @default.
• W4383821461 creator A5047143588 @default.
• W4383821461 creator A5054294894 @default.
• W4383821461 creator A5058271316 @default.
• W4383821461 creator A5059561650 @default.
• W4383821461 creator A5069013086 @default.
• W4383821461 creator A5079751395 @default.
• W4383821461 date "2023-07-10" @default.
• W4383821461 modified "2023-10-10" @default.
• W4383821461 title "An amino acid-resolution interactome for motile cilia illuminates the structure and function of ciliopathy protein complexes" @default.
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