Key result
Cryo-EM and simulations resolve F-actin-bound Myo5a structure, predicting a 35 nm working stroke.
Why the study?
Little is known about the structure and physical properties of the myosin 5a lever and how they contribute to walking mechanics.
Cryo-EM and MD simulations reveal the physical properties of the Myo5a lever, predicting a 35 nm working stroke and providing new insights into its walking behavior.
Myosin 5a (Myo5a) is a dimeric processive motor protein that transports cellular cargos along filamentous actin (F-actin). Its long lever is responsible for its large power-stroke, step size, and load-bearing ability. Little is known about the levers' structure and physical properties, and how they contribute to walking mechanics. Using cryoelectron microscopy (cryo-EM) and molecular dynamics (MD) simulations, we resolved the structure of monomeric Myo5a, comprising the motor domain and full-length lever, bound to F-actin. The range of its lever conformations revealed its physical properties, how stiffness varies along its length and predicts a large, 35 nm, working stroke. Thus, the newly released trail head in a dimeric Myo5a would only need to perform a small diffusive search for its new binding site on F-actin, and stress would only be generated across the dimer once phosphate is released from the lead head, revealing new insight into the walking behavior of Myo5a.
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Gravett et al. (2024) studied this question. Cryo-EM and molecular dynamics simulations resolved the structure of monomeric Myo5a bound to F-actin, revealing lever stiffness variations and predicting a large 35 nm working stroke.
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