Graduate School of Frontier Biosciences, Osaka University, and Riken Quantitative Biology Center, 1-3 Yamadaoka, Suita, Osaka 565-0871, Japan.
Nat Commun. 2017 Jan 9;8:13969. doi: 10.1038/ncomms13969.
Muscle contraction is driven by cyclic association and dissociation of myosin head of the thick filament with thin actin filament coupled with ATP binding and hydrolysis by myosin. However, because of the absence of actomyosin rigour structure at high resolution, it still remains unclear how the strong binding of myosin to actin filament triggers the release of hydrolysis products and how ATP binding causes their dissociation. Here we report the structure of mammalian skeletal muscle actomyosin rigour complex at 5.2 Å resolution by electron cryomicroscopy. Comparison with the structures of myosin in various states shows a distinctly large conformational change, providing insights into the ATPase-coupled reaction cycle of actomyosin. Based on our observations, we hypothesize that asymmetric binding along the actin filament could function as a Brownian ratchet by favouring directionally biased thermal motions of myosin and actin.
肌肉收缩是由肌球蛋白头部与细肌动蛋白丝的周期性结合和解离驱动的，同时伴随着肌球蛋白与 ATP 的结合和水解。然而，由于在高分辨率下缺乏肌球蛋白与肌动蛋白丝的坚韧结构，因此仍然不清楚肌球蛋白与肌动蛋白丝的强结合如何触发水解产物的释放，以及 ATP 结合如何导致它们的解离。在这里，我们通过电子冷冻显微镜报告了哺乳动物骨骼肌肌球蛋白坚韧复合物在 5.2Å分辨率下的结构。与各种状态下的肌球蛋白结构进行比较显示出明显的大构象变化，为肌球蛋白与肌动球蛋白的 ATP 酶偶联反应循环提供了深入了解。基于我们的观察，我们假设沿肌动蛋白丝的不对称结合可以作为布朗棘轮，通过有利于肌球蛋白和肌动蛋白的定向偏热运动。
