Direct observation shows superposition and large scale flexibility within cytoplasmic dynein motors moving along microtubules

Hiroshi Imai, Tomohiro Shima, Kazuo Sutoh, Matthew L. Walker, Peter J. Knight (), Takahide Kon and Stan A. Burgess
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Hiroshi Imai: School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds
Tomohiro Shima: Quantitative Biology Center
Kazuo Sutoh: Faculty of Science and Engineering, Waseda University
Matthew L. Walker: MLW Consulting
Peter J. Knight: School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds
Takahide Kon: Graduate School of Science, Osaka University
Stan A. Burgess: School of Molecular and Cellular Biology and Astbury Centre for Structural Molecular Biology, Faculty of Biological Sciences, University of Leeds

Nature Communications, 2015, vol. 6, issue 1, 1-11

Abstract: Abstract Cytoplasmic dynein is a dimeric AAA+ motor protein that performs critical roles in eukaryotic cells by moving along microtubules using ATP. Here using cryo-electron microscopy we directly observe the structure of Dictyostelium discoideum dynein dimers on microtubules at near-physiological ATP concentrations. They display remarkable flexibility at a hinge close to the microtubule binding domain (the stalkhead) producing a wide range of head positions. About half the molecules have the two heads separated from one another, with both leading and trailing motors attached to the microtubule. The other half have the two heads and stalks closely superposed in a front-to-back arrangement of the AAA+ rings, suggesting specific contact between the heads. All stalks point towards the microtubule minus end. Mean stalk angles depend on the separation between their stalkheads, which allows estimation of inter-head tension. These findings provide a structural framework for understanding dynein’s directionality and unusual stepping behaviour.

Date: 2015
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DOI: 10.1038/ncomms9179

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