Terada Tomoki P, Sasai Masaki, Yomo Tetsuya
Graduate School of Human Informatics, Nagoya University, Nagoya 464-8601, Japan.
Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9202-6. doi: 10.1073/pnas.132711799. Epub 2002 Jun 24.
Actin-myosin (actomyosin) generates mechanical force by consuming ATP molecules. We apply the energy landscape perspective to address a controversial issue as to whether the myosin head moves with multiple steps after a single ATP hydrolysis or only a single mechanical event of the lever-arm swinging follows a single ATP hydrolysis. Here we propose a theoretical model in which the refolding of the partially unfolded actomyosin complex and the movement of the myosin head along the actin filament are coupled. A single ATP hydrolysis is followed by the formation of a high free-energy partially unfolded actomyosin complex, which then gradually refolds with a concomitant multiple stepping movement on the way to the lowest free-energy rigor state. The model quantitatively explains the single-molecular observation of the multiple stepping movement and is consistent with structural observations of the disorder in the actomyosin-binding process. The model also explains the observed variety in dwell time before each step, which is not accounted for by previous models, such as the lever-arm or ratchet models.
肌动蛋白-肌球蛋白（肌动球蛋白）通过消耗ATP分子产生机械力。我们运用能量景观视角来解决一个有争议的问题，即肌球蛋白头部在一次ATP水解后是进行多步移动，还是一次ATP水解仅伴随着杠杆臂摆动这一单一机械事件。在此，我们提出一个理论模型，其中部分展开的肌动球蛋白复合物的重新折叠与肌球蛋白头部沿肌动蛋白丝的移动是耦合的。一次ATP水解后会形成一个高自由能的部分展开的肌动球蛋白复合物，该复合物随后在向最低自由能强直状态转变的过程中逐渐重新折叠，并伴随着多步移动。该模型定量解释了多步移动的单分子观测结果，并且与肌动球蛋白结合过程中无序状态的结构观测结果一致。该模型还解释了所观察到的每一步之前停留时间的变化，而先前的模型，如杠杆臂模型或棘轮模型，并未对此做出解释。
