Lever-arm mechanics of processive myosins.
Lever-arm mechanics of processive myosins.
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进行性肌球蛋白的杠杆臂力学。
DOI：
10.1016/j.bpj.2011.05.026
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发表时间：
2011
影响因子：
3.4
通讯作者：
Goldman,YaleE
中科院分区：
文献类型：
--
作者：
Sun,Yujie;Goldman,YaleE
肌球蛋白超家族的成员在细胞中执行多种运输、组装、锚定和信号传导功能 (1-29)。它们共享保守的运动域，通常位于 N 末端，结合肌动蛋白丝，水解 ATP，并将化学能转化为机械能。肌球蛋白马达具有高度可变的尾部结构域，可能通过与货物和膜蛋白的特异性结合与其在细胞中的定位和功能有关 (10-12、15、30-34)。加工肌球蛋白马达通常是二聚体，其尾部结构域以卷曲螺旋 (CC) 连接。运动域和尾部域之间是所谓的肌球蛋白颈或杠杆臂域，通常认为其参与运动调节和/或充当旋转或倾斜的杠杆，以将运动域中的埃级构象变化放大为纳米级的动力冲程运动。颈结构域或轻链结构域 (LCD) 通常在重链相对较长的 a 螺旋片段中的连续共有基序（IQ 结构域 (1)）处结合钙调蛋白或钙调蛋白样轻链 (35)（下文均称为 CaM）。通常认为杠杆的长度是由每个肌球蛋白亚型中结合的 IQ 基序和 CaM 的数量决定的。然而，这一假设受到了多种证据的挑战，这些证据表明重链的其他部分表现出机械刚度并且也有助于动力冲程。如果将杠杆臂视为肌球蛋白电机的一部分，对应于工作冲程期间倾斜的机械部分，则可以将其定义为三个区域的组合：1）转换器（电机域 C 末端的旋转子域）； 2)、CaM结合LCD区域； 3) LCD 和 CC 之间重链的任何段，如果该段是刚性的 (36)。非常规肌球蛋白已分为 30 多个不同的类别（5、14、16、37）。它们的结构、功能和调节已被广泛描述和回顾（1-10、12-17、20-29、33、37-50）。在对这些肌球蛋白的深入研究中，电机的颈部区域具有与其作为杠杆臂的功能一致的特性：它们在迈步期间在两个主要方向之间来回倾斜（51-56），运动的步长和速度取决于颈部的长度（40、47、57-60），并且在连接到人工颈部区域的结构中，运动方向取决于人工附件的方向（61）。在这篇小综述中，我们考虑了三种肌球蛋白（肌球蛋白 V、VI 和 X）的特殊杠杆臂结构以及这些结构对这些肌球蛋白的步进特性和功能的影响。我们在这里重点关注颈部区域作为机械杠杆臂的作用，尽管它们也参与调节运动（45、62）和（可能）感知张力（42、49、63-65）。对于肌球蛋白 VI 和 X，存在关于杠杆臂的长度和组成及其对其路径、角运动和持续过程的影响的开放研究问题。
Members of the myosin superfamily perform a wide variety of transport, assembly, anchoring, and signaling functions in cells (1–29). They share conserved motor domains, usually located at the N-terminus, that bind actin filaments, hydrolyze ATP, and convert the chemical energy into mechanical work. Myosin motors have highly variable tail domains that presumably are related to their localizations and functions in the cell through specific binding to cargos and membrane proteins (10–12, 15, 30–34). Processive myosin motors are usually dimers whose tail domains are linked in a coiledcoil (CC). Between the motor domain and the tail domain is the so-called myosin neck or lever-arm domain, which is generally believed to be involved in motor regulation and/or to act as a lever that rotates or tilts to amplify the angstrom-level conformational changes in the motor domain to the nanometer-sized power-stroke motions. The neck domain, or light chain domain (LCD), usually binds calmodulin or calmodulin-like light chains (35)(both termed CaM hereafter) at successive consensus motifs (IQ domains (1)) in a relatively long a-helical segment of the heavy chain. The length of the lever has often been assumed to be determined by the number of IQ motifs and CaMs bound in each myosin isoform. However, this assumption has been challenged by many types of evidence that other portions of the heavy chain exhibit mechanical stiffness and also contribute to the power stroke. If the lever arm is instead considered as the portion of a myosin motor that corresponds to the mechanical segment that tilts during the working stroke, it can be defined as a combination of three regions: 1), the converter (the rotating subdomain at the C-terminus of the motor domain); 2), the CaM-binding LCD region; and 3), any segment of the heavy chain between LCD and the CC, if that segment is stiff (36). Unconventional myosins have been categorized into more than 30 distinct classes (5, 14, 16, 37). Their structure, function, and regulation have been described and reviewed extensively (1–10, 12–17, 20–29, 33, 37–50). In the best studied of these myosins, the neck regions of the motor have properties consistent with their function as lever arms: they tilt back and forth between two main orientations during stepping (51–56), the step size and velocity of motility depend on the length of the neck (40, 47, 57–60), and in constructs attached to artificial neck regions, the direction of motion depends on the orientation of the artificial attachment (61). In this mini-review, we consider the specialized lever-arm structures of three myosins (myosins V, VI, and X) and the impact these structures have on the stepping characteristics and functions of these myosins. We focus here on the role of the neck regions as mechanical lever arms, although they are also involved in regulating motility (45, 62) and (possibly) sensing tension (42, 49, 63–65). For myosins VI and X, there are open research questions regarding the length and composition of the lever arms and the consequent implications for their paths, angular motions, and processivity.
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影响因子：
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作者：
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影响因子：
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