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The 2.8 Å crystal structure of the dynein motor domain

Abstract

Dyneins are microtubule-based AAA+ motor complexes that power ciliary beating, cell division, cell migration and intracellular transport. Here we report the most complete structure obtained so far, to our knowledge, of the 380-kDa motor domain of Dictyostelium discoideum cytoplasmic dynein at 2.8 Å resolution; the data are reliable enough to discuss the structure and mechanism at the level of individual amino acid residues. Features that can be clearly visualized at this resolution include the coordination of ADP in each of four distinct nucleotide-binding sites in the ring-shaped AAA+ ATPase unit, a newly identified interaction interface between the ring and mechanical linker, and junctional structures between the ring and microtubule-binding stalk, all of which should be critical for the mechanism of dynein motility. We also identify a long-range allosteric communication pathway between the primary ATPase and the microtubule-binding sites. Our work provides a framework for understanding the mechanism of dynein-based motility.

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Figure 1: Overall structure of the dynein motor domain.
Figure 2: Structure of the four nucleotide-binding sites.
Figure 3: Linker–ring interactions.
Figure 4: Structure and function of stalk–strut and C sequence.
Figure 5: Proposed mechanism underlying dynein’s motor actions.

Accession codes

Primary accessions

Protein Data Bank

Data deposits

Coordinates and structure factors have been deposited in the Protein Data Bank under accession numbers 3VKG (ΔMTBD) and 3VKH (wild type).

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Acknowledgements

We thank E. Yamashita, Y. Umena, M. Suzuki and A. Nakagawa of SPring-8 BL-44XU for their support during X-ray data collection; and T. Kikuchi and R. Ohkura for their technical support. We are grateful to C. Toyoshima for discussion of X-ray data collection; K. Kinosita Jr and T. Tsukihara for their support and encouragement. This work was supported by Grants-in-Aid for Scientific Research (17770126, 20687011 and 23370073 (T.K.), 16083205 and 17107003 (K.S.), 17053006, 18054008 and 20051006 (G.K.)) from the Ministry of Education, Culture Sports, Science, and Technology of Japan and a grant from the Human Frontier Science Program (T.K.).

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T.K., K.S. and G.K. designed the study. T.K. purified, crystallized and collected X-ray data; T.O. and G.K. processed and refined X-ray data; T.K, R.S.-K, K.I. and T.S. performed functional analyses; T.K., K.S. and G.K. wrote the paper. All authors discussed the results and commented on the manuscript.

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Correspondence to Takahide Kon.

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The authors declare no competing financial interests.

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Kon, T., Oyama, T., Shimo-Kon, R. et al. The 2.8 Å crystal structure of the dynein motor domain. Nature 484, 345–350 (2012). https://doi.org/10.1038/nature10955

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