Article | Published:

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

Nature volume 554, pages 202206 (08 February 2018) | Download Citation

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.

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Acknowledgements

We thank S. Scheres, X. Bai, K. Vinothkumar and R. Leiro for cryo-EM advice; S. Chen, G. McMullan, C. Savva, G. Cannone, J. Grimmett and T. Darling for technical support; S. Bullock for SNAPf–dynein (1-1074-GST); M. Yu for crystallography support and the European Synchrotron Radiation Facility (beamline ID29) for data collection; T. Croll for model building; S. Bullock, L. Passmore, S. Lacey and H. Foster for manuscript comments; and G. Lander for discussions. This work was funded by Wellcome Trust (WT100387) and MRC grants (MC_UP_A025_1011) to A.P.C.; and NIH (GM094522) and NSF (MCB-1055017, MCB-1617028) grants to A.Y.

Author information

Author notes

    • Carina Motz

    Present address: Department Chemie, Technische Universität München (TUM), Lichtenbergstrasse 4, 85747, Garching, Germany.

    • Linas Urnavicius
    •  & Clinton K. Lau

    These authors contributed equally to this work.

Affiliations

  1. Medical Research Council Laboratory of Molecular Biology, Division of Structural Studies, Francis Crick Avenue, Cambridge CB2 0QH, UK

    • Linas Urnavicius
    • , Clinton K. Lau
    • , Carina Motz
    •  & Andrew P. Carter
  2. Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA

    • Mohamed M. Elshenawy
    •  & Ahmet Yildiz
  3. Department of Biochemistry, CINVESTAV, México D.F., Mexico

    • Edgar Morales-Rios
  4. Physics Department, University of California at Berkeley, Berkeley, California 94720, USA

    • Ahmet Yildiz

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Contributions

L.U. performed all cryo-EM work on TDR, and C.K.L. performed all cryo-EM work on TDH. L.U., C.K.L., M.M.E and A.P.C. performed single-molecule experiments. L.U. performed negative-stain electron microscopy. M.M.E. and A.Y. performed optical trapping. E.M.-R. determined the NDD structure. C.M. made dynein (1-1455). A.P.C., L.U. and C.K.L. built and refined the TDR model and prepared the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Andrew P. Carter.

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Extended data

Supplementary information

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  1. 1.

    Life Sciences Reporting Summary

Videos

  1. 1.

    The dynein tail/dynactin/BICDR1 complex

    The full dynein tail/dynactin/BICDR1 complex (PDB:6F1T) is shown with the dynein tails (blue and red) and BICDR1 (yellow) shown in cartoon representation, and dynactin shown in surface representation (green). The complex is rotated, first to show the heavy chains in the grooves along dynactin’s filament, then to show interactions between the dynein tails and BICDR1.

  2. 2.

    The cascade of dynein/dynein interactions

    This video starts by focusing in on the two dynein tails from PDB 6F1T. Dynein interactions are then shown in sphere representation (colored according to Fig. 5b and Extended Data Fig. 7b). The complex is rocked to show the extensive interactions between dynein chains.

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DOI

https://doi.org/10.1038/nature25462

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