Goychuk Igor
Institute for Physics and Astronomy, University of Potsdam, Karl-Liebknecht-Str. 24/25, D-14476 Potsdam-Golm, Germany.
Phys Biol. 2015 Jan 30;12(1):016013. doi: 10.1088/1478-3975/12/1/016013.
Here we generalize our previous model of molecular motors trafficking subdiffusing cargos in viscoelastic cytosol by (i) including mechano-chemical coupling between cyclic conformational fluctuations of the motor protein driven by the reaction of ATP hydrolysis and its translational motion within the simplest two-state model of hand-over-hand motion of kinesin, and also (ii) by taking into account the anharmonicity of the tether between the motor and the cargo (its maximally possible extension length). It is shown that the major earlier results such as occurrence of normal versus anomalous transport depending on the amplitude of binding potential, cargo size and the motor turnover frequency not only survive in this more realistic model, but the results also look very similar for the correspondingly adjusted parameters. However, this more realistic model displays a substantially larger thermodynamic efficiency due to a bidirectional mechano-chemical coupling. For realistic parameters, the maximal thermodynamic efficiency can transiently be about 50% as observed for kinesins, and even larger, surprisingly also in a novel strongly anomalous (sub)transport regime, where the motor enzymatic turnovers become also anomalously slow and cannot be characterized by a turnover rate. Here anomalously slow dynamics of the cargo enforces anomalously slow cyclic kinetics of the motor protein.
在此,我们推广了之前关于分子马达在粘弹性胞质溶胶中运输亚扩散货物的模型,具体方式为:(i)在驱动蛋白最简单的手换手运动两态模型中,纳入由ATP水解反应驱动的马达蛋白周期性构象波动与其平移运动之间的机械化学耦合;(ii)考虑马达与货物之间系链的非谐性(其最大可能伸长长度)。结果表明,早期的主要结果,如取决于结合势振幅、货物大小和马达周转频率的正常运输与反常运输的出现,不仅在这个更现实的模型中仍然成立,而且对于相应调整后的参数,结果看起来也非常相似。然而,由于双向机械化学耦合,这个更现实的模型显示出显著更高的热力学效率。对于实际参数,最大热力学效率可以瞬间达到约50%,如在驱动蛋白中观察到的那样,甚至更高,令人惊讶的是,在一种新的强反常(亚)运输 regime中也是如此,在这种情况下,马达酶促周转也变得异常缓慢,无法用周转率来表征。在这里,货物的异常缓慢动力学导致马达蛋白的异常缓慢循环动力学。