Key result
Myosin 5a lever exhibits variable stiffness that accommodates a ~35-nm working stroke.
Why the study?
Little is known about the physical properties of the myosin 5a lever and how they contribute to the mechanics of walking.
This high-resolution structure of the myosin 5a lever provides fundamental biophysical insights into its flexibility, directional isotropy, and stepping mechanics along actin filaments.
Findings remain preclinical; leaves open whether lever mechanics influence human cellular transport or disease.
Myosin 5a transports cellular cargos along actin filaments towards the cell periphery. Its long lever plays a key role in determining the large size of its powerstoke, stepping distance along F-actin, ability to bear load and its regulation by Ca 2+ . Despite this, little is known about the physical properties of the lever and how they contribute to the mechanics of walking. Using a combination of cryo-electron microscopy and molecular dynamics simulations, we resolved the first structure of myosin 5a comprising the motor domain and full-length lever (subfragment-1) bound to actin. From the flexibility captured in the cryo-electron microscopy data, we were able to characterise the stiffness of the lever. Here, we demonstrate how the structure and flexibility of the lever contribute to the regulation and walking behaviour of myosin 5a.
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Gravett et al. (2023) studied this question. Myosin 5a structure analysis via cryo-EM was evaluated on Structure and physical properties of the myosin 5a lever. Cryo-EM structures and molecular dynamics simulations of myosin 5a revealed variable stiffness along its full-length lever and accommodated a working stroke of approximately 35 nm.
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