Myosin structure and function.
Myosin structure and function.
复制标题
肌球蛋白的结构和功能。
DOI：
10.1101/sqb.1995.060.01.084
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
T. Uyeda
中科院分区：
文献类型：
--
作者：
J. Spudich;J. Finer;B. Simmons;K. Ruppel;B. Patterson;T. Uyeda
在过去的十年里，人们对分子马达的兴趣激增，很明显，肌动蛋白马达和微管马达构成了一个大家族，其成员在细胞中执行不同的功能（Vale 1992; Goldstein 1993; Mooseker 1993）。在过去的十年中，人们在遗传和分子遗传学方法方面的努力不断增加，这些方法揭示了许多形式的细胞运动和细胞形状变化的分子基础（Vale 1992; Goldstein 1993; Spudich 1994）。此外，已经开发了用于在体外测量纯化的分子马达的运动的方法，并且这些方法已经允许定义分子马达功能的关键参数（对于综述，参见Spudich 1994）。在这里，我们集中在第一个确定的和最好的特点的分子马达超家族成员，传统的肌球蛋白分子，这是第一次在肌肉中发现的世纪。这种常规肌球蛋白由两条高分子量重链和两对轻链组成，每条重链约为200，000道尔顿，两对轻链称为必需轻链（ELC）和调节轻链（RLC）。这些亚基一起组装成由两个球状头部结构域和一个α-螺旋卷曲螺旋尾部组成的六聚体（图1A）。尾部参与肌球蛋白组装成粗丝，这对肌肉收缩和非肌肉运动都是必不可少的。球状头部结构域，称为亚片段-1（S1），包含必需和调节轻链，在1987年被证明足以在ATP驱动下体外运动肌动蛋白丝（Toyoshima et al. 1987），从那时起，工作集中在理解S1产生的能量转导的分子基础上。1993年测定了S1的晶体结构（图1B）（Rayment等，1993 b），极大地促进了这一领域的进一步实验。尽管对肌肉收缩以及肌动蛋白和肌球蛋白的生物化学进行了数十年的研究，但对于肌动蛋白和肌球蛋白相互作用产生的运动发生方式，仍然存在三种明显不同的模型。最流行的模型是摆动横桥模型（Huxley 1969; Huxley and Simmons 1971），热棘轮概念是一种可能的详细机制的具体描述（Huxley 1957; Vale and Oosawa 1990）。然而，哈灵顿和他的同事（哈灵顿1971）提供的证据表明，肌球蛋白尾部的螺旋卷曲转变可以提供收缩所需的动力和位移，这个模型在20世纪80年代得到了非常认真的考虑。当在体外运动性测定中显示球状头部结构域是运动所需的全部时，该模型几乎被排除。第三类模型涉及肌动蛋白丝结构的传播变化作为运动的驱动力，由肌球蛋白头与肌动蛋白的相互作用引起（Yanagida et al. 1985; Harada et al. 1990，Schutt and Lindberg 1993）。根据这个模型，肌动蛋白是马达，而不是肌球蛋白分子。
There has been an explosion of interest in molecular motors in the last decade, and it is clear that both the actin-based motors and the microtubule-based motors constitute large families, members of which carry out distinct functions in the cell (Vale 1992; Goldstein 1993; Mooseker 1993). This last decade has witnessed an increased effort in genetic and molecular genetic approaches that have revealed the molecular basis of a number of forms of cell movement and changes in cell shape (Vale 1992; Goldstein 1993; Spudich 1994). In addition, methods have been developed for measuring the movement of purified molecular motors in vitro, and these methods have allowed the definition of critical parameters of molecular motor function (for review, see Spudich 1994). Here we focus on the firstidentified and best-characterized member of the molecular motor superfamily, the conventional myosin molecule, which was first discovered in muscle in the 19th century. This conventional myosin consists of two high-molecular-weight heavy chains of about 200,000 daltons each and two pairs of light chains, known as the essential light chain (ELC) and the regulatory light chain (RLC). These subunits are assembled together into a hexamer that consists of two globular head domains and an a-helical coiled-coil tail (Fig. 1A). The tail is involved in assembly of myosin into thick filaments that are essential for both muscle contraction and nonmuscle movements. The globular head domains, called subfragment-1 (S1), which contain the essential and regulatory light chains, were shown in 1987 to be sufficient for ATP-driven in vitro motility of actin filaments (Toyoshima et al. 1987), and since then, work has focused on understanding the molecular basis of energy transduction produced by S1. The determination of the crystal structure of S1 (Fig. 1B) in 1993 (Rayment et al. 1993b) has greatly facilitated further experimentation in this area. Despite decades of research on muscle contraction and the biochemistry of actin and myosin, there remain three clearly distinct models for the way in which movement occurs, generated by the interaction of actin and myosin. The most popular model has been the swinging crossbridge model (Huxley 1969; Huxley and Simmons 1971), the thermal ratchet concept being one specific description of a possible detailed mechanism (Huxley 1957; Vale and Oosawa 1990). However, Harrington and his colleagues (Harrington 1971) provided evidence that a helix coil transition in the myosin tail could provide the motive force and displacement required for contraction, and this model was very seriously considered in the 1980s. This model was all but ruled out when it was shown that the globular head domain was all that was needed for movement in in vitro motility assays. The third class of model involves propagated changes in the aetin filament structure as the driving force for the motion, induced by the interaction of the myosin head with the actin (Yanagida et al. 1985; Harada et al. 1990, Schutt and Lindberg 1993). According to this model, the actin is the motor, rather than the myosin molecule.