Kinematics of the lever arm swing in myosin VI

Proceedings of the National Academy of Sciences of the United States of America
Mauro L Mugnai, D Thirumalai

Abstract

Myosin VI (MVI) is the only known member of the myosin superfamily that, upon dimerization, walks processively toward the pointed end of the actin filament. The leading head of the dimer directs the trailing head forward with a power stroke, a conformational change of the motor domain exaggerated by the lever arm. Using a unique coarse-grained model for the power stroke of a single MVI, we provide the molecular basis for its motility. We show that the power stroke occurs in two major steps. First, the motor domain attains the poststroke conformation without directing the lever arm forward; and second, the lever arm reaches the poststroke orientation by undergoing a rotational diffusion. From the analysis of the trajectories, we discover that the potential that directs the rotating lever arm toward the poststroke conformation is almost flat, implying that the lever arm rotation is mostly uncoupled from the motor domain. Because a backward load comparable to the largest interhead tension in a MVI dimer prevents the rotation of the lever arm, our model suggests that the leading-head lever arm of a MVI dimer is uncoupled, in accord with the inference drawn from polarized total internal reflection fluorescence (polTIRF) experiments....Continue Reading

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Citations

Sep 12, 2019·Proceedings of the National Academy of Sciences of the United States of America·Wonmuk Hwang, Martin Karplus
Sep 13, 2017·Proceedings of the National Academy of Sciences of the United States of America·Raphael Alhadeff, Arieh Warshel
Aug 4, 2019·International Journal of Molecular Sciences·Nidhi Singh, Wenjin Li
May 6, 2020·Biophysical Journal·Mauro L MugnaiD Thirumalai
Dec 7, 2018·Current Opinion in Structural Biology·Alexander J Pak, Gregory A Voth
May 7, 2021·Journal of Chemical Information and Modeling·Ai ShinobuYuji Sugita
Jul 13, 2021·Journal of Chemical Theory and Computation·Yonathan Goldtzvik, D Thirumalai
Aug 14, 2018·The Journal of Physical Chemistry. B·Jie Chen, D Thirumalai

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