A simulation model of the conventional kinesin based on the Driven-by-Detachment mechanism

Kinesins are molecular motors that unidirectionally move along microtubules using the chemical energy of ATP. Although the core structure of kinesins is similar to that of myosins, the lever-arm hypothesis, which is widely accepted as a plausible mechanism to explain the behaviors of myosins, cannot be directly applied to kinesins. Masuda has proposed a mechanochemical process called the 'Driven-by-Detachment (DbD)' mechanism to explain the characteristic behaviors of myosins, including the backward movement of myosin VI and the loose coupling phenomenon of myosin II. The DbD mechanism assumes that the energy of ATP is mainly used to detach a myosin head from an actin filament by temporarily reducing the affinity of the myosin against the actin. After the affinity is recovered, the detached head has potential energy originating from the attractive force between the myosin and the actin. During the docking process, the potential energy is converted into elastic energy within the myosin molecule, and the intramolecular elastic energy is finally used to produce the power strokes. In the present paper, the DbD mechanism was used to explain the hand-over-hand motion of the conventional kinesin. The neck linker of the kinesin is known to determine the directionality of the motility but, in this paper, it was assumed that the neck linker was not directly engaged in the power strokes, which were driven by the attractive force between the kinesin head and the microtubule. Based on this assumption, simple mechanical simulations showed that the model of a kinesin dimer processively moved along a microtubule protofilament, if the affinity of the kinesin against the microtubule is appropriately controlled. Moreover, if an external force was applied to the center of the kinesin dimer, the dimer moved backward along a microtubule, as observed in experimental motility assays.

[1]  Hernando Sosa,et al.  Nucleotide binding and hydrolysis induces a disorder-order transition in the kinesin neck-linker region , 2006, Nature Structural &Molecular Biology.

[2]  M. Schnitzer,et al.  Force production by single kinesin motors , 2000, Nature Cell Biology.

[3]  R. Vale,et al.  Kinesin Walks Hand-Over-Hand , 2004, Science.

[4]  E. Mandelkow,et al.  The Crystal Structure of Dimeric Kinesin and Implications for Microtubule-Dependent Motility , 1997, Cell.

[5]  Joshua W. Shaevitz,et al.  Probing the kinesin reaction cycle with a 2D optical force clamp , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[6]  K C Holmes,et al.  Structural mechanism of muscle contraction. , 1999, Annual review of biochemistry.

[7]  R. Vale,et al.  The way things move: looking under the hood of molecular motor proteins. , 2000, Science.

[8]  Tadashi Masuda.  An electromechanical model of myosin molecular motors. , 2003, Journal of theoretical biology.

[9]  Mark J. Schnitzer,et al.  Kinesin hydrolyses one ATP per 8-nm step , 1997, Nature.

[10]  Tadashi Masuda.  A deterministic mechanism producing the loose coupling phenomenon observed in an actomyosin system , 2009, Biosyst..

[11]  Christoph F. Schmidt,et al.  Direct observation of kinesin stepping by optical trapping interferometry , 1993, Nature.

[12]  Robert A Cross,et al.  The kinetic mechanism of kinesin. , 2004, Trends in biochemical sciences.

[13]  Michael A. Geeves,et al.  Molecular motors: Stretching the lever-arm theory , 2002, Nature.

[14]  Toshio Yanagida,et al.  Sliding distance of actin filament induced by a myosin crossbridge during one ATP hydrolysis cycle , 1985, Nature.

[15]  Roger Cooke,et al.  A structural change in the kinesin motor protein that drives motility , 1999, Nature.

[16]  Ronald D Vale,et al.  The Directional Preference of Kinesin Motors Is Specified by an Element outside of the Motor Catalytic Domain , 1997, Cell.

[17]  W. Schief,et al.  Conformational changes during kinesin motility. , 2001, Current opinion in cell biology.

[18]  L. Amos.  Molecular motors: rocking and rolling , 2005, Nature chemical biology.

[19]  D. Hackney,et al.  Evidence for alternating head catalysis by kinesin during microtubule-stimulated ATP hydrolysis. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[20]  R. Cross,et al.  Mechanics of the kinesin step , 2005, Nature.

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

[22]  Tadashi Masuda,et al.  A possible mechanism for determining the directionality of myosin molecular motors , 2008, Biosyst..

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

[24]  Toshio Yanagida,et al.  Single molecule thermodynamics in biological motors , 2007, Biosyst..

[25]  R Vale,et al.  Thermodynamic properties of the kinesin neck-region docking to the catalytic core. , 2003, Biophysical journal.

[26]  M. F. Stock,et al.  Modulation of kinesin half-site ADP release and kinetic processivity by a spacer between the head groups. , 2003, Biochemistry.

[27]  C. Asbury.  Kinesin: world's tiniest biped. , 2005, Current opinion in cell biology.

[28]  Roger Cooke,et al.  Two conformations in the human kinesin power stroke defined by X-ray crystallography and EPR spectroscopy , 2002, Nature Structural Biology.

[29]  J. Gelles,et al.  Coupling of kinesin steps to ATP hydrolysis , 1997, Nature.

[30]  Toshio Yanagida,et al.  A single myosin head moves along an actin filament with regular steps of 5.3 nanometres , 1999, Nature.

[31]  Ronald D. Vale,et al.  Crystal structure of the kinesin motor domain reveals a structural similarity to myosin , 1996, Nature.

[32]  T. Yanagida,et al.  Entropy rectifies the Brownian steps of kinesin , 2005, Nature chemical biology.