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Title: De novo identification of mammalian ciliary motility proteins using cryo-EM
Authors: Gui, Miao
Farley, Hannah
Anujan, Priyanka
Anderson, Jacob R.
Maxwell, Dale W.
Whitchurch, Jonathan B.
Botsch, J. Josephine
Qiu, Tao
Meleppattu, Shimi
Singh, Sandeep K.
Zhang, Qi
Thompson, James
Lucas, Jane S.
Bingle, Colin D.
Norris, Dominic P.
Roy, Sudipto 
Brown, Alan
Keywords: axonemal dyneins
ciliary motility
doublet microtubules
microtubule inner proteins
Issue Date: 1-Nov-2021
Publisher: Elsevier B.V.
Citation: Gui, Miao, Farley, Hannah, Anujan, Priyanka, Anderson, Jacob R., Maxwell, Dale W., Whitchurch, Jonathan B., Botsch, J. Josephine, Qiu, Tao, Meleppattu, Shimi, Singh, Sandeep K., Zhang, Qi, Thompson, James, Lucas, Jane S., Bingle, Colin D., Norris, Dominic P., Roy, Sudipto, Brown, Alan (2021-11-01). De novo identification of mammalian ciliary motility proteins using cryo-EM. Cell 184 (23). ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Dynein-decorated doublet microtubules (DMTs) are critical components of the oscillatory molecular machine of cilia, the axoneme, and have luminal surfaces patterned periodically by microtubule inner proteins (MIPs). Here we present an atomic model of the 48-nm repeat of a mammalian DMT, derived from a cryoelectron microscopy (cryo-EM) map of the complex isolated from bovine respiratory cilia. The structure uncovers principles of doublet microtubule organization and features specific to vertebrate cilia, including previously unknown MIPs, a luminal bundle of tektin filaments, and a pentameric dynein-docking complex. We identify a mechanism for bridging 48- to 24-nm periodicity across the microtubule wall and show that loss of the proteins involved causes defective ciliary motility and laterality abnormalities in zebrafish and mice. Our structure identifies candidate genes for diagnosis of ciliopathies and provides a framework to understand their functions in driving ciliary motility. © 2021 The Author(s)
Source Title: Cell
ISSN: 0092-8674
DOI: 10.1016/j.cell.2021.10.007
Rights: Attribution 4.0 International
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