Article

Force production by single kinesin motors.

Biological Computation Research Department, Bell Laboratories, Lucent Technologies, Murray Hill, New Jersey 07974, USA.
Nature Cell Biology (Impact Factor: 20.06). 11/2000; 2(10):718-23. DOI: 10.1038/35036345
Source: PubMed

ABSTRACT Motor proteins such as kinesin, myosin and polymerase convert chemical energy into work through a cycle that involves nucleotide hydrolysis. Kinetic rates in the cycle that depend upon load identify transitions at which structural changes, such as power strokes or diffusive motions, are likely to occur. Here we show, by modelling data obtained with a molecular force clamp, that kinesin mechanochemistry can be characterized by a mechanism in which a load-dependent isomerization follows ATP binding. This model quantitatively accounts for velocity data over a wide range of loads and ATP levels, and indicates that movement may be accomplished through two sequential 4-nm substeps. Similar considerations account for kinesin processivity, which is found to obey a load-dependent Michaelis-Menten relationship.

1 Follower
 · 
65 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Kinesin is a smart motor protein that steps processively forward and backward along microtubules (MTs). The mechanical kinetics of kinesin affecting its stepping behavior is not fully understood. Here, we propose a mathematical model to study the mechanical kinetics of forward and backward stepping of kinesin motor based on the four-state discrete stochastic model of the motor. Results show that the probabilities of forward and backward stepping can be modeled using the mean probabilities of forward and backward kinetic transitions, respectively. We show that the backward stepping of kinesin motor starts when the probability of ADP binding to the motor is much higher than that of ATP binding. Furthermore, our results indicate that the backward stepping of kinesin motor is related to both ATP hydrolysis and synthesis with rate limiting factor being ATP synthesis. Very low rate of ATP synthesis under high backward loads above 10 pN is also suggested as a reason for the detachment of kinesin motor from MT in the kinetic state MT·Kinesin·ADP·Pi. a.liew@griffith.edu.au.
    Bioinformatics 11/2013; 30(3). DOI:10.1093/bioinformatics/btt698 · 4.62 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Intracellular cargos that are transported by groups of molecular motors often display bidirectional movement. This can be seen experimentally by tracking the trajectories of individual cargos in vivo. Typically, the cargo trajectories display many turning events that result from the stochastic nature of the involved motor processes. In this paper, we simulate cargo trajectories for different binding mechanisms. We introduce a series of statistical tools to analyze and quantitatively characterize these trajectories. As we demonstrate for specified single-motor properties, the novel statistical methods allow us to quantitatively distinguish between different models for bidirectional transport. In this way, the tools provide a quantitative connection between the statistical properties of the cargo trajectories and the molecular properties of the motor proteins. Such methods are also applicable to experimentally measured cargo trajectories and should be helpful in elucidating the mechanisms that lead to bidirectional transport.
    Physical Biology 01/2013; 10(1):016003. DOI:10.1088/1478-3975/10/1/016003 · 3.14 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We describe a system of stochastic differential equations (SDEs) which model the interaction between processive molecular motors, such as kinesin and dynein, and the biomolecular cargo they tow as part of microtubule-based intracellular transport. We show that the classical experimental environment fits within a parameter regime which is qualitatively distinct from conditions one expects to find in living cells. Through an asymptotic analysis of our system of SDEs, we develop a means for applying in vitro observations of the nonlinear response by motors to forces induced on the attached cargo to make analytical predictions for two parameter regimes that have thus far eluded direct experimental observation: (1) highly viscous in vivo transport and (2) dynamics when multiple identical motors are attached to the cargo and microtubule.
    Journal of Theoretical Biology 04/2012; 305:54-69. DOI:10.1016/j.jtbi.2012.03.035 · 2.30 Impact Factor

Preview

Download
1 Download
Available from