Department of Physics, Cornell University, Ithaca, United States.
Department of Physics and Astronomy, Denison University, Granville, United States.
Elife. 2020 Jan 15;9:e51569. doi: 10.7554/eLife.51569.
The molecular motor myosin V transports cargo by stepping on actin filaments, executing a random diffusive search for actin binding sites at each step. A recent experiment suggests that the joint between the myosin lever arms may not rotate freely, as assumed in earlier studies, but instead has a preferred angle giving rise to structurally constrained diffusion. We address this controversy through comprehensive analytical and numerical modeling of myosin V diffusion and stepping. When the joint is constrained, our model reproduces the experimentally observed diffusion, allowing us to estimate bounds on the constraint energy. We also test the consistency between the constrained diffusion model and previous measurements of step size distributions and the load dependence of various observable quantities. The theory lets us address the biological significance of the constrained joint and provides testable predictions of new myosin behaviors, including the stomp distribution and the run length under off-axis force.
分子马达肌球蛋白 V 通过在肌动蛋白丝上踩踏来运输货物，在每一步执行随机扩散搜索肌动蛋白结合位点。最近的一项实验表明，肌球蛋白杠杆臂之间的连接处可能不像早期研究中假设的那样可以自由旋转，而是具有一个优先角度，导致结构受限扩散。我们通过对肌球蛋白 V 扩散和步进的全面分析和数值建模来解决这一争议。当接头受到限制时，我们的模型再现了实验观察到的扩散，使我们能够估计限制能量的范围。我们还测试了受限扩散模型与之前测量的步长分布以及各种可观察量的负载依赖性之间的一致性。该理论使我们能够解决受约束接头的生物学意义，并对新的肌球蛋白行为提供可测试的预测，包括 stomp 分布和在非轴向力下的运行长度。
