Mechanics of actomyosin bonds in different nucleotide states are tuned to muscle contraction
Mechanics of actomyosin bonds in different nucleotide states are tuned to muscle contraction
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DOI：
10.1073/pnas.0601255103
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发表时间：
2006-06-27
影响因子：
11.1
通讯作者：
Guilford, William H.
中科院分区：
文献类型：
--
作者：
Guo, Bin;Guilford, William H.
肌肉收缩和许多其他细胞运动是由肌动蛋白丝和运动酶肌球蛋白之间的循环相互作用驱动的。肌动蛋白-肌球蛋白结合界面的构象变化与 ATP 的结合、与肌动蛋白的结合以及水解副产物的损失同时发生，但这些构象变化对肌动球蛋白键强度的影响尚不清楚。肌动球蛋白键的力依赖性动力学在高负载下可能特别重要，其中肌球蛋白可能在实现其完整动力冲程之前与肌动蛋白分离。在这里，我们表明，在快速施加负载的生理范围内，肌动球蛋白表现为“捕获”键，其特征是随着负载增加至最大约 6 pN，寿命增加。令人惊讶的是，我们发现肌球蛋白-ADP键在负载下比刚性键具有更长的寿命，尽管键寿命最大时的负载保持不变。我们还发现肌动球蛋白键寿命最终不仅取决于负载，还取决于负载历史。这些数据表明肌动球蛋白解离速率与肌肉力量和缩短速度之间存在复杂的关系。最大键寿命的 6-pN 负载接近等长收缩期间单个肌球蛋白分子产生的力。这提出了一种可能性，即承载分子之间的所有捕获键都“机械动力学”地调整到它们的生理环境。
Muscle contraction and many other cell movements are driven by cyclic interactions between actin filaments and the motor enzyme myosin. Conformational changes in the actin-myosin binding interface occur in concert with the binding of ATP, binding to actin, and loss of hydrolytic by-products, but the effects of these conformational changes on the strength of the actomyosin bond are unknown. The force-dependent kinetics of the actomyosin bond may be particularly important at high loads, where myosin may detach from actin before achieving its full power stroke. Here we show that over a physiological range of rapidly applied loads, actomyosin behaves as a "catch" bond, characterized by increasing lifetimes with increasing loads up to a maximum at approximate to 6 pN. Surprisingly, we found that the myosin-ADP bond is possessed of longer lifetimes under load than rigor bonds, although the load at which bond lifetime is maximal remains unchanged. We also found that actomyosin bond lifetime is ultimately dependent not only on load, but loading history as well. These data suggest a complex relationship between the rate of actomyosin dissociation and muscle force and shortening velocity. The 6-pN load for maximum bond lifetime is near the force generated by a single myosin molecule during isometric contraction. This raises the possibility that all catch bonds between load-bearing molecules are "mechanokinetically" tuned to their physiological environment.