Key result
A 3D reconstruction of the switched-off 10S form of myosin II revealed multiple interactions between the tail and the two heads that block actin binding, obstruct head phosphorylation, and prevent filament formation.
Why the study?
The mechanism of inhibition of the inactive folded monomer conformation of myosin II is not fully understood.
The 3D structure of 10S myosin reveals how tail-head interactions inhibit myosin function, explaining its energy-conserving storage role in cells.
Answers are grounded in this paper and cite their sources.
Elucidates myosin auto-inhibition mechanism; leaves open translation to human cardiovascular therapies.
Myosin II is a motor protein playing an essential role in cell motility. The molecule can exist as a polymer that pulls on actin to generate motion, or as an inactive monomer with a compact structure, in which its tail is folded and its two heads interact with each other. This conformation functions in cells as an energy-conserving storage and transport molecule. The mechanism of inhibition is not fully understood. We have carried out a 3D reconstruction of the switched-off form revealing for the first time multiple interactions between the tail and the two heads that trap ATP hydrolysis products, block actin binding, obstruct head phosphorylation, and prevent filament formation. Blocking these essential features of myosin function can explain the high degree of inhibition of the folded form of myosin, serving its energy-conserving, storage function in cells. The structure also suggests a mechanism for unfolding when activated by phosphorylation.
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Yang et al. (2019) studied Myosin II structure and function. 10S smooth muscle myosin was evaluated on 3D structure and intramolecular interactions. A 3D reconstruction of the switched-off 10S form of myosin II revealed multiple interactions between the tail and the two heads that block actin binding, obstruct head phosphorylation, and prevent filament formation.
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