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bioRxiv · 10.1101/2020.12.08.415687

Cryo-EM structures of outer-arm dynein array bound to microtubule doublet reveal a mechanism for motor coordination

Zhang, K.·Rao, Q.·Wang, Y.·Chai, P.·Kuo, Y.-W.·Han, L.·Yang, R.·Yang, Y.·Howard, J.
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Abstract

Thousands of outer-arm dyneins (OADs) are arrayed in the axoneme to drive a rhythmic ciliary beat. Coordination among multiple OADs is essential for generating mechanical forces to bend microtubule doublets (MTDs). Using electron microscopy, we determined high-resolution structures of OAD arrays bound to MTD in two different states. OAD preferentially binds to MTD protofilaments with a pattern resembling the native tracks for its distinct microtubule-binding domains. Upon MTD binding, free OADs are induced to adopt a stable parallel conformation, primed for array formation. Extensive tail-to-head (TTH) interactions between OADs are observed, which need to be broken for ATP turnover by the dynein motor. We propose that OADs in an array sequentially hydrolyze ATP to slide MTDs. ATP-hydrolysis in turn relaxes the TTH interfaces to effectuate free nucleotide cycles of downstream OADs. These findings lead to a model explaining how conformational changes in the axoneme produce coordinated action of dyneins.

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Zhang, K., Rao, Q., Wang, Y., Chai, P., Kuo, Y.-W., Han, L., Yang, R., Yang, Y., Howard, J.. 2020-12-08. Cryo-EM structures of outer-arm dynein array bound to microtubule doublet reveal a mechanism for motor coordination. https://doi.org/10.1101/2020.12.08.415687

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