Davis J S
Biophys J. 1986 Sep;50(3):417-22. doi: 10.1016/S0006-3495(86)83477-4.
A mechanism for length regulation in the parallel-packed section of the thick filament is proposed. It is based on experiments done on synthetic, mini- and native filaments, and its primary purpose is to explain the physical basis of the kinetic mechanism for the assembly of synthetic thick filaments from myosin alone. Kinetically, length is regulated by a dissociation rate constant that increases exponentially as the filament grows bi-directionally from its center. Growth ceases at the point of equilibrium between invariant on and length-dependent off rates. The three subfilaments structure of the parallel-packed region of the thick filament is fundamental to the proposed scheme. The intra-subfilament bonding is strong and predominantly ionic in character, whereas the inter-subfilament bonding is relatively weak. These strong and weak interactions participate directly in the strictly sequential mechanism of assembly of dimer subunit observed in the kinetics. A third domain, independent of the sequential mechanism, consists of opposing negative charges on the subfilament surface, juxtaposed at or close to the thick filament axis. The weak and repulsive domains are additively coupled to each other through the rigidity in the subfilaments. Length regulation occurs through the repulsive component rising in intensity more rapidly with length than the initially stronger positive interactions. Growth ceases at the point where the repulsive interactions weaken the attractive interactions to the extent that equilibrium is established between head-to-tail dimer subunit and its binding sites at the tips of the arms of thick filament. This myosin-mediated mechanism, which gives rise to a narrow length distribution, is considered to be fine-tuned by co-polymerizing proteins to give the precise length of the native filament.
提出了一种粗肌丝平行堆积部分长度调节的机制。它基于对合成丝、微型丝和天然丝所做的实验，其主要目的是解释仅由肌球蛋白组装合成粗肌丝动力学机制的物理基础。从动力学角度来看，长度由解离速率常数调节，该常数随着丝从其中心双向生长而呈指数增加。生长在不变的结合速率和长度依赖性解离速率之间的平衡点处停止。粗肌丝平行堆积区域的三股亚丝结构是所提出方案的基础。亚丝内的键合很强且主要是离子性的，而亚丝间的键合相对较弱。这些强相互作用和弱相互作用直接参与了动力学中观察到的二聚体亚基组装的严格顺序机制。第三个结构域独立于顺序机制，由亚丝表面相对的负电荷组成，这些负电荷在粗肌丝轴处或其附近并列。弱的排斥结构域通过亚丝的刚性相互加性耦合。长度调节是通过排斥成分强度随长度增加的速度比最初更强的正向相互作用更快来实现的。当排斥相互作用削弱吸引相互作用到一定程度，即在粗肌丝臂末端的头尾二聚体亚基与其结合位点之间建立平衡时，生长停止。这种由肌球蛋白介导的机制会产生狭窄的长度分布，被认为通过与共聚蛋白共同聚合来进行微调，以产生天然丝的精确长度。
