Structural Basis for Microtubule Binding and Release by Dynein

Science  21 Sep 2012:
Vol. 337, Issue 6101, pp. 1532-1536
DOI: 10.1126/science.1224151

You are currently viewing the abstract.

View Full Text
As a service to the community, AAAS/Science has made this article free with registration.


Cytoplasmic dynein is a microtubule-based motor required for intracellular transport and cell division. Its movement involves coupling cycles of track binding and release with cycles of force-generating nucleotide hydrolysis. How this is accomplished given the ~25 nanometers separating dynein’s track- and nucleotide-binding sites is not understood. Here, we present a subnanometer-resolution structure of dynein’s microtubule-binding domain bound to microtubules by cryo–electron microscopy that was used to generate a pseudo-atomic model of the complex with molecular dynamics. We identified large rearrangements triggered by track binding and specific interactions, confirmed by mutagenesis and single-molecule motility assays, which tune dynein’s affinity for microtubules. Our results provide a molecular model for how dynein’s binding to microtubules is communicated to the rest of the motor.

View Full Text