The Zhang group, in collaboration the Howard group, published seminal findings on the structure of outer-arm dynein arrays bound to microtubules in Nature Structural & Molecular Biology. Zhang et al. proposed that the coordinated action of dyneins depend on conformational changes in the axoneme to drive a ciliary beat. Titled “Structures of outer-arm dynein array on microtubule doublet reveal a motor coordination mechanism,” the work also recently received the Gibbons Gold Award.
Eukaryotic cilia are crucial drivers of cell movement and are involved in the transport of extracellular fluids. The beating of motile cilia depends on microtubule-based molecular motors called dyneins, which hydrolyze ATP to slide along microtubules. The two main classes of dyneins include inner-arm dyneins (IAD) and outer-arm dyneins (OAD). In the axoneme, OAD molecules form ordered arrays that coordinate to produce rhythms of the ciliary beat. Understanding the mechanism of motor coordination between adjacent OADs has been a long-standing question in the cilium field.
Using the model organism T. thermophila, Zhang et al. solved high-resolution cryo-EM structures of OAD arrays bound to microtubule doublets (MTDs) in two different states. The group found that OADs adopt a tail-to-head conformation that stimulates the formation of arrays. These arrays are primed to hydrolyze ATP and slide MTDs, which disrupts the OAD interface to free nucleotide cycles of downstream OADs. The OADs sequentially change their conformations to take one step along the MTD toward the minus ends. Importantly, this work contributes toward understanding – in near atomic detail- how OAD arrays on MTD coordinate to drive ciliary action.
The study was led by co-first authors Qinhui Rao, Long Han, Yue Wang, and Pengxin Chai and can be found on the Nature website: https://www.nature.com/articles/s41594-021-00656-9.
By Brigitte Naughton