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

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.09.548259v1?rss=1 Authors: McCafferty, C. L., Papoulas, O., Lee, C., Bui, K. H. L., Taylor, D. W., Marcotte, E. M., Wallingford, J. B. 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 27,000 XLs, we identified 9,208 unique amino acid interactions among 1,368 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. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC