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Cryo-EM shows how dynactin recruits two dyneins for faster movement

Author

Listed:
  • Linas Urnavicius

    (Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue)

  • Clinton K. Lau

    (Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue)

  • Mohamed M. Elshenawy

    (University of California at Berkeley)

  • Edgar Morales-Rios

    (CINVESTAV)

  • Carina Motz

    (Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue
    Technische Universität München (TUM))

  • Ahmet Yildiz

    (University of California at Berkeley
    University of California at Berkeley)

  • Andrew P. Carter

    (Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue)

Abstract

Dynein and its cofactor dynactin form a highly processive microtubule motor in the presence of an activating adaptor, such as BICD2. Different adaptors link dynein and dynactin to distinct cargoes. Here we use electron microscopy and single-molecule studies to show that adaptors can recruit a second dynein to dynactin. Whereas BICD2 is biased towards recruiting a single dynein, the adaptors BICDR1 and HOOK3 predominantly recruit two dyneins. We find that the shift towards a double dynein complex increases both the force and speed of the microtubule motor. Our 3.5 Å resolution cryo-electron microscopy reconstruction of a dynein tail–dynactin–BICDR1 complex reveals how dynactin can act as a scaffold to coordinate two dyneins side-by-side. Our work provides a structural basis for understanding how diverse adaptors recruit different numbers of dyneins and regulate the motile properties of the dynein–dynactin transport machine.

Suggested Citation

  • Linas Urnavicius & Clinton K. Lau & Mohamed M. Elshenawy & Edgar Morales-Rios & Carina Motz & Ahmet Yildiz & Andrew P. Carter, 2018. "Cryo-EM shows how dynactin recruits two dyneins for faster movement," Nature, Nature, vol. 554(7691), pages 202-206, February.
  • Handle: RePEc:nat:nature:v:554:y:2018:i:7691:d:10.1038_nature25462
    DOI: 10.1038/nature25462
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    Cited by:

    1. Ricardo Celestino & Morkos A Henen & José B Gama & Cátia Carvalho & Maxwell McCabe & Daniel J Barbosa & Alexandra Born & Parker J Nichols & Ana X Carvalho & Reto Gassmann & Beat Vögeli, 2019. "A transient helix in the disordered region of dynein light intermediate chain links the motor to structurally diverse adaptors for cargo transport," PLOS Biology, Public Library of Science, vol. 17(1), pages 1-33, January.
    2. Kyoko Okada & Bharat R. Iyer & Lindsay G. Lammers & Pedro A. Gutierrez & Wenzhe Li & Steven M. Markus & Richard J. McKenney, 2023. "Conserved roles for the dynein intermediate chain and Ndel1 in assembly and activation of dynein," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. John T. Canty & Andrew Hensley & Merve Aslan & Amanda Jack & Ahmet Yildiz, 2023. "TRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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