A Kinetic Model Describing the Processivity of Myosin-V

Skau, Karl Isak; Hoyle, Rebecca B.; Turner, Matthew S.

doi:10.1529/biophysj.105.070888

Cited by 28 publications

(62 citation statements)

References 49 publications

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“…Searching a 25-dimensional space is an intrinsically difficult problem. We used a Monte Carlo strategy (Materials and Methods) (37,38). A cost function quantified the least-squares difference between the data of Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The four-state model has 25 free parameters, precluding a deterministic search or mapping of the parameter space. We adapted a Monte Carlo search strategy (38), using simplex optimization to find local minima starting from randomly generated points in parameter space. We defined a cost function to determine the quality of fit to experimental data for each parameter set, both during and after the simplex optimization, Err ¼ ∑X:…”

Section: Methodsmentioning

confidence: 99%

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Mechanism and kinetics of a sodium-driven bacterial flagellar motor

Sowa

Pilizota

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

104

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The bacterial flagellar motor is a large rotary molecular machine that propels swimming bacteria, powered by a transmembrane electrochemical potential difference. It consists of an ∼50-nm rotor and up to ∼10 independent stators anchored to the cell wall. We measured torque-speed relationships of single-stator motors under 25 different combinations of electrical and chemical potential. All 25 torque-speed curves had the same concave-down shape as fully energized wild-type motors, and each stator passes at least 37 ± 2 ions per revolution. We used the results to explore the 25-dimensional parameter space of generalized kinetic models for the motor mechanism, finding 830 parameter sets consistent with the data. Analysis of these sets showed that the motor mechanism has a "powerstroke" in either ion binding or transit; ion transit is channel-like rather than carrier-like; and the rate-limiting step in the motor cycle is ion binding at low concentration, ion transit, or release at high concentration. where V m is the membrane voltage and Δμ = k B T ln(C in /C out ) and q are the transmembrane chemical potential difference and charge of the ions, respectively, with C in and C out the internal and external ion concentrations. In most species the primary form of biological free energy is the proton-motive force (PMF), the IMF for H + ions (1). Physiological PMF is typically in the range −150 mV to −200 mV, with the inside electrically negative and slightly alkaline relative to the outside. Some organisms use sodium-motive force (SMF) to drive numerous cellular processes, such as bacterial motility (2), ATP synthesis (3), and active membrane transport (4). Arguably the most important process driven by IMF is ATP synthesis, which generates cellular ATP by forced rotation of the F 1 part of F 1 F O ATP-synthase. F 1 is mechanically coupled to and rotated by F O , which like the bacterial flagellar motor (BFM) is an ion-driven rotary motor. Understanding the mechanism of these and other ion-driven molecular machines is a fundamental challenge in cellular energetics and biophysics. The BFM (Fig. 1A) is a rotary molecular machine that propels many species of swimming bacteria. It couples ion flow, for example protons (H + ) in Escherichia coli or sodium ions (Na + ) in Vibrio alginolyticus, to the rotation of extracellular helical flagellar filaments at hundreds of revolutions per second (Hz) (2, 5, 6). Torque is generated by interactions between stator complexes (containing the proteins MotA and MotB in E. coli and PomA and PomB in V. alginolyticus) and the rotor protein FliG (7). In E. coli, each motor can be powered by any number between 1 and at least 11 functionally independent stators (8), which exchange with a membrane-bound pool of "spare" stators on a timescale of minutes (9).The most important biophysical method for studying the torque-generating mechanism of the BFM has been to measure its torque-speed curves. This has been done using varying viscous load (10-14) or external torque (15, 16) to control the speed. Fu...

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Mechanism and kinetics of a sodium-driven bacterial flagellar motor

Sowa

Pilizota

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

104

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“…Myosin head functions through its ATPase reaction as a force generator and as a mechanosensor, and two myosin heads work together in moving along an actin filament which is involved in a wide range of transport and contractile activities in cells (59,60).…”

Section: Myosin Head Domain Containing Proteinmentioning

confidence: 99%

Effects of a surface topography composite with puerariae radix on human STRO-1-positive stem cells

et al. 2010

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“…The large persistence length l p of the lever arms (26)(27)(28) allows us to propose a coarse-grained polymer model for the reaction-diffusion problem, which, in turn, yields approximate analytical expressions for all the physical observables, including binding times, run length, velocity, and stall force. We have built on the insights of earlier theoretical works (28)(29)(30)(31)(32)(33)(34), which focused on modeling a reaction network of discrete states in the mechanochemical cycle of the motor heads. Our work supplements the reaction network with an explicit treatment of the diffusive search, which has been studied using insightful Brownian dynamics simulations of forward stepping in MyoV (35).…”

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confidence: 99%

Design principles governing the motility of myosin V

Hinczewski

Tehver

Thirumalai

2013

Proc. Natl. Acad. Sci. U.S.A.

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The molecular motor myosin V (MyoV) exhibits a wide repertoire of pathways during the stepping process, which is intimately connected to its biological function. The best understood of these is the hand-over-hand stepping by a swinging lever arm movement toward the plus end of actin filaments. Single-molecule experiments have also shown that the motor "foot stomps," with one hand detaching and rebinding to the same site, and back-steps under sufficient load. The complete taxonomy of MyoV's load-dependent stepping pathways, and the extent to which these are constrained by motor structure and mechanochemistry, are not understood. Using a polymer model, we develop an analytical theory to describe the minimal physical properties that govern motor dynamics. We solve the first-passage problem of the head reaching the target-binding site, investigating the competing effects of backward load, strain in the leading head biasing the diffusion in the direction of the target, and the possibility of preferential binding to the forward site due to the recovery stroke. The theory reproduces a variety of experimental data, including the power stroke and slow diffusive search regimes in the mean trajectory of the detached head, and the force dependence of the forward-to-backward step ratio, run length, and velocity. We derive a stall force formula, determined by lever arm compliance and chemical cycle rates. By exploring the MyoV design space, we predict that it is a robust motor whose dynamical behavior is not compromised by reasonable perturbations to the reaction cycle and changes in the architecture of the lever arm.functional robustness | polymer physics | architectural basis | stall force expression M yosin V (MyoV), a cytoskeletal motor protein belonging to the myosin superfamily (1), converts energy from ATP hydrolysis into the transport of intracellular cargo, such as mRNA and organelles along actin filaments (2). In its dimeric form, the motor has two actin-binding, ATPase heads connected to α-helical lever arm domains stiffened by attached calmodulins or essential light chains (Fig. 1). The nucleotide-driven mechanochemical cycle of the heads produces two changes in the lever arm orientation: a power stroke, where an actin-bound head swings the lever arm forward toward the plus (barbed) end of the filament, and a recovery stroke, which returns the arm to its original configuration when the head is detached from actin (3). The motor translates these changes into processive plus end-directed movement (4-6). By alternating head detachment, MyoV walks hand-over-hand (7,8), taking one step of ≈36 nm for each ATP consumed (9). At small loads, the motor can complete ≈20 − 60 forward steps before dissociating from actin (6, 10, 11). Such a high unidirectional processivity requires coordination in the detachment of the two heads, a "gating" mechanism, which is believed to arise from the strain within the molecule when both heads are bound to actin (12-15). Sufficiently large opposing loads can counteract the plus end-directed ...

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A Kinetic Model Describing the Processivity of Myosin-V

Cited by 28 publications

References 49 publications

Mechanism and kinetics of a sodium-driven bacterial flagellar motor

Mechanism and kinetics of a sodium-driven bacterial flagellar motor

Effects of a surface topography composite with puerariae radix on human STRO-1-positive stem cells

Design principles governing the motility of myosin V

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