The requirement for mechanical coupling between head and S2 domains in smooth muscle myosin ATPase regulation and its implications for dimeric motor function
The requirement for mechanical coupling between head and S2 domains in smooth muscle myosin ATPase regulation and its implications for dimeric motor function
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DOI：
10.1016/j.jmb.2004.10.084
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发表时间：
2005-01-28
影响因子：
5.6
通讯作者：
Taylor, KA
中科院分区：
文献类型：
--
作者：
Tama, F;Feig, M;Taylor, KA
实验结构数据，同源建模和弹性网络正常模式分析的组合被用来探索如何耦合运动之间的两个肌球蛋白头和二聚化结构域（S2）在平滑肌肌球蛋白11确定域运动所需的实现抑制状态的ATP依赖的分子马达。这些物理模型合理化的经验要求，至少两个heptads的非卷曲的α-螺旋之间的连接处的肌球蛋白头和S2，和依赖于S2长度的调节。结果与改变构象依赖的溶解度和稳定性的生化数据相关。推定的活性状态和抑制状态之间的构象转变的结构模型表明，扭转灵活性的S2 α-螺旋是肌球蛋白11调节的关键机械要求。肌球蛋白头部围绕其卷曲螺旋α-螺旋的这些扭转运动影响S2结构域结构，其间接影响肌球蛋白头部的运动。这种相互关系可以解释大量关于通过卷曲螺旋结构域形成二聚体的分子马达功能的数据。(C)2004爱思唯尔有限公司保留所有权利。
A combination of experimental structural data, homology modelling and elastic network normal mode analysis is used to explore how coupled motions between the two myosin heads and the dimerization domain (S2) in smooth muscle myosin 11 determine the domain movements required to achieve the inhibited state of this ATP-dependent molecular motor. These physical models rationalize the empirical requirement for at least two heptads of non-coiled a-helix at the junction between the myosin heads and S2, and the dependence of regulation on S2 length. The results correlate well with biochemical data regarding altered conformational-dependent solubility and stability. Structural models of the conformational transition between putative active states and the inhibited state show that torsional flexibility of the S2 a-helices is a key mechanical requirement for myosin 11 regulation. These torsional motions of the myosin heads about their coiled coil a-helices affect the S2 domain structure, which reciprocally affects the motions of the myosin heads. This inter-relationship may explain a large body of data on function of molecular motors that form dimers through a coiled-coil domain. (C) 2004 Elsevier Ltd. All rights reserved.