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Integrated modeling of the Nexin-dynein regulatory complex reveals its regulatory mechanism

Author

Listed:
  • Avrin Ghanaeian

    (McGill University)

  • Sumita Majhi

    (Nencki Institute of Experimental Biology of Polish Academy of Sciences)

  • Caitlyn L. McCafferty

    (University of Texas)

  • Babak Nami

    (Hospital for Sick Children)

  • Corbin S. Black

    (McGill University)

  • Shun Kai Yang

    (McGill University)

  • Thibault Legal

    (McGill University)

  • Ophelia Papoulas

    (University of Texas)

  • Martyna Janowska

    (Nencki Institute of Experimental Biology of Polish Academy of Sciences
    Mossakowski Institute of Experimental and Clinical Medicine, Polish Academy of Science)

  • Melissa Valente-Paterno

    (McGill University)

  • Edward M. Marcotte

    (University of Texas)

  • Dorota Wloga

    (Nencki Institute of Experimental Biology of Polish Academy of Sciences)

  • Khanh Huy Bui

    (McGill University)

Abstract

Cilia are hairlike protrusions that project from the surface of eukaryotic cells and play key roles in cell signaling and motility. Ciliary motility is regulated by the conserved nexin-dynein regulatory complex (N-DRC), which links adjacent doublet microtubules and regulates and coordinates the activity of outer doublet complexes. Despite its critical role in cilia motility, the assembly and molecular basis of the regulatory mechanism are poorly understood. Here, using cryo-electron microscopy in conjunction with biochemical cross-linking and integrative modeling, we localize 12 DRC subunits in the N-DRC structure of Tetrahymena thermophila. We also find that the CCDC96/113 complex is in close contact with the DRC9/10 in the linker region. In addition, we reveal that the N-DRC is associated with a network of coiled-coil proteins that most likely mediates N-DRC regulatory activity.

Suggested Citation

  • Avrin Ghanaeian & Sumita Majhi & Caitlyn L. McCafferty & Babak Nami & Corbin S. Black & Shun Kai Yang & Thibault Legal & Ophelia Papoulas & Martyna Janowska & Melissa Valente-Paterno & Edward M. Marco, 2023. "Integrated modeling of the Nexin-dynein regulatory complex reveals its regulatory mechanism," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-41480-7
    DOI: 10.1038/s41467-023-41480-7
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    1. Daniel Russel & Keren Lasker & Ben Webb & Javier Velázquez-Muriel & Elina Tjioe & Dina Schneidman-Duhovny & Bret Peterson & Andrej Sali, 2012. "Putting the Pieces Together: Integrative Modeling Platform Software for Structure Determination of Macromolecular Assemblies," PLOS Biology, Public Library of Science, vol. 10(1), pages 1-5, January.
    2. Jianfeng Lin & Weining Yin & Maria C. Smith & Kangkang Song & Margaret W. Leigh & Maimoona A. Zariwala & Michael R. Knowles & Lawrence E. Ostrowski & Daniela Nicastro, 2014. "Cryo-electron tomography reveals ciliary defects underlying human RSPH1 primary ciliary dyskinesia," Nature Communications, Nature, vol. 5(1), pages 1-10, December.
    3. Ivan Iossifov & Brian J. O’Roak & Stephan J. Sanders & Michael Ronemus & Niklas Krumm & Dan Levy & Holly A. Stessman & Kali T. Witherspoon & Laura Vives & Karynne E. Patterson & Joshua D. Smith & Brya, 2014. "The contribution of de novo coding mutations to autism spectrum disorder," Nature, Nature, vol. 515(7526), pages 216-221, November.
    4. Shintaroh Kubo & Corbin S. Black & Ewa Joachimiak & Shun Kai Yang & Thibault Legal & Katya Peri & Ahmad Abdelzaher Zaki Khalifa & Avrin Ghanaeian & Caitlyn L. McCafferty & Melissa Valente-Paterno & Ch, 2023. "Native doublet microtubules from Tetrahymena thermophila reveal the importance of outer junction proteins," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
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