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 Tetrahymena thermophila OAD arrays bound to MTDs 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 the MTDs. ATP hydrolysis in turn relaxes the TTH interfaces to effect free nucleotide cycles of downstream OADs. These findings lead to a model explaining how conformational changes in the axoneme produce coordinated action of dyneins.
Highlights
Thousands of outer-arm dyneins (OADs) are arrayed in the axoneme to drive a rhythmic ciliary beat
The tail is permanently attached to the microtubule doublets (MTDs) A-tubule, while the head region of each heavy chains (HCs) contains a microtubule-binding domain (MTBD), which binds and releases the MTD B-tubule depending on the nucleotide states (Fig. 1a)[8,9,10,11,12]
After demembranation and high salt treatment on the purified axoneme, the MTD was enriched by centrifugation and OAD was purified by sucrose-gradient ultracentrifugation followed by ion exchange for all subsequent biochemical and structural analyses (Fig. 1b,c and Extended Data Fig. 1)
Summary
Thousands of outer-arm dyneins (OADs) are arrayed in the axoneme to drive a rhythmic ciliary beat. Two rows of axonemal dyneins, the OADs and inner-arm dyneins (IADs), power the ciliary beating by sliding the adjacent MTDs. OAD is the key motor protein that generates the majority of mechanical forces required for this fundamental cellular process[7]. Cryo-electron tomography (cryo-ET) studies suggest that adjacent OADs are indirectly connected to each other via a series of linker structures[13,14] It remains unclear how OAD arrays are formed and why they are important for ciliary beat. In combination with previously reported cryo-ET structures, we propose a model for how OADs coordinate with each other to move one step on the MTD, and how ciliary beat is propagated
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