Laboratoire de Chimie Biophysique, ISIS, Université de Strasbourg, 67000 Strasbourg, France.
Structure. 2010 Mar 14;18(4):458-70. doi: 10.1016/j.str.2010.01.014.
The release of phosphate (Pi) is an important element in actomyosin function and has been shown to be accelerated by the binding of myosin to actin. To provide information about the structural elements important for Pi release, possible escape pathways from various isolated myosin II structures have been determined by molecular dynamics simulations designed for studying such slow processes. The residues forming the pathways were identified and their role was evaluated by mutant simulations. Pi release is slow in the pre-powerstroke structure, an important element in preventing the powerstroke prior to actin binding, and is much more rapid for Pi modeled into the post-rigor and rigor-like structures. The previously proposed backdoor route is dominant in the pre-powerstroke and post-rigor states, whereas a different path is most important in the rigor-like state. This finding suggests a mechanism for the actin-activated acceleration of Pi release.
磷酸盐（Pi）的释放是肌球蛋白功能的一个重要元素，已被证明通过肌球蛋白与肌动蛋白的结合而加速。为了提供有关释放 Pi 的重要结构元素的信息，通过设计用于研究此类缓慢过程的分子动力学模拟，确定了来自各种分离的肌球蛋白 II 结构的可能逃逸途径。鉴定了形成途径的残基，并通过突变体模拟评估了它们的作用。在预功结构中 Pi 的释放非常缓慢，这是防止肌动蛋白结合前进行功结构的重要元素，而在后僵直和类似僵直的结构中 Pi 的释放则快得多。先前提出的后门途径在预功和后僵直状态中占主导地位，而在类似僵直状态中最重要的是不同的途径。这一发现为肌动蛋白激活加速 Pi 释放的机制提供了线索。
