Mechanochemical model for myosin V

A rigorous numerical test of a hypothetical mechanism of a molecular motor should model explicitly the diffusive motion of the motor's degrees of freedom as well as the transition rates between the motor's chemical states. We present such a Brownian dynamics, mechanochemcial model of the coarse-grain structure of the dimeric, linear motor myosin V. Compared with run-length data, our model provides strong support for a proposed strain-controlled gating mechanism that enhances processivity. We demonstrate that the diffusion rate of a detached motor head during motor stepping is self-consistent with known kinetic rate constants and can explain the motor's key performance features, such as speed and stall force. We present illustrative and realistic animations of motor stepping in the presence of thermal noise. The quantitative success and illustrative power of this type of model suggest that it will be useful in testing our understanding of a range of biological and synthetic motors.

[1]  Gerhard A Blab,et al.  The Tumbleweed: Towards a synthetic protein motor , 2009, HFSP journal.

[2]  S. Block,et al.  Direct Observation of Individual Kinesin Head Motions , 2009 .

[3]  A. Vilfan Five models for myosin V. , 2008, Frontiers in bioscience.

[4]  Hailong Lu,et al.  Myosin V and Kinesin act as tethers to enhance each others' processivity , 2008, Proceedings of the National Academy of Sciences.

[5]  J. Ross,et al.  Cargo transport: molecular motors navigate a complex cytoskeleton. , 2008, Current opinion in cell biology.

[6]  M. Rief,et al.  Myosin V stepping mechanism , 2007, Proceedings of the National Academy of Sciences.

[7]  Kazuhiko Kinosita,et al.  Myosin V Walks by Lever Action and Brownian Motion , 2007, Science.

[8]  A. Dunn,et al.  Dynamics of the unbound head during myosin V processive translocation , 2007, Nature Structural &Molecular Biology.

[9]  Kenneth A. Taylor,et al.  Three-dimensional structure of the myosin V inhibited state by cryoelectron tomography , 2006, Nature.

[10]  Matthias Rief,et al.  Myosin-V is a mechanical ratchet. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[11]  J. Spudich,et al.  From the Cover : A force-dependent state controls the coordination of processive myosin V , 2005 .

[12]  Roberto Dominguez,et al.  Structure of the light chain-binding domain of myosin V. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[13]  K. Trybus No strain, no gain , 2005, Nature Cell Biology.

[14]  J. Sellers,et al.  Load-dependent kinetics of myosin-V can explain its high processivity , 2005, Nature Cell Biology.

[15]  E. Krementsova,et al.  Differential labeling of myosin V heads with quantum dots allows direct visualization of hand-over-hand processivity. , 2005, Biophysical journal.

[16]  A. Vilfan Elastic lever-arm model for myosin V. , 2005, Biophysical journal.

[17]  Sean X. Sun,et al.  Dynamics of myosin-V processivity. , 2005, Biophysical journal.

[18]  Francis Lin,et al.  Intracellular actin-based transport: how far you go depends on how often you switch. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Shin'ichi Ishiwata,et al.  Mechanochemical coupling of two substeps in a single myosin V motor , 2004, Nature Structural &Molecular Biology.

[20]  J. Baker,et al.  Myosin V processivity: multiple kinetic pathways for head-to-head coordination. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[21]  Paul R. Selvin,et al.  Myosin V Walks Hand-Over-Hand: Single Fluorophore Imaging with 1.5-nm Localization , 2003, Science.

[22]  Yale E. Goldman,et al.  Three-dimensional structural dynamics of myosin V by single-molecule fluorescence polarization , 2003, Nature.

[23]  J. Sellers,et al.  The prepower stroke conformation of myosin V , 2002, The Journal of cell biology.

[24]  C. Yengo,et al.  Kinetic characterization of the weak binding states of myosin V. , 2002, Biochemistry.

[25]  David M. Warshaw,et al.  Myosin V exhibits a high duty cycle and large unitary displacement , 2001, The Journal of cell biology.

[26]  Amber L. Wells,et al.  Actin and light chain isoform dependence of myosin V kinetics. , 2000, Biochemistry.

[27]  A. Mehta,et al.  Myosin-V stepping kinetics: a molecular model for processivity. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[28]  John Trinick,et al.  Two-headed binding of a processive myosin to F-actin , 2000, Nature.

[29]  Amber L. Wells,et al.  The kinetic mechanism of myosin V. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[30]  Matthias Rief,et al.  Myosin-V is a processive actin-based motor , 1999, Nature.

[31]  P. Forscher,et al.  Brain myosin-V is a two-headed unconventional myosin with motor activity , 1993, Cell.

[32]  Justin E. Molloy,et al.  The gated gait of the processive molecular motor, myosin V , 2002, Nature Cell Biology.