Offer G, Knight P
Department of Clinical Veterinary Science, The University of Bristol, UK.
J Mol Biol. 1996 Mar 1;256(3):407-16. doi: 10.1006/jmbi.1996.0096.
An atomic model of the junction between the two heads and tail of a myosin molecule has been created by attaching a scallop regulatory domain to the end of each of the two alpha-helical strands of a model of the scallop alpha-helical coiled coil. The C-terminal alpha-helix of the heavy chain of each regulatory domain was superposed over the corresponding sequence in the coiled coil. In the structure created, the two heads lie alongside one another with their bases in contact but remarkably without steric clash. The principal interactions between the two heads are between the regulatory light chains and there are also head-tail interactions between each regulatory light chain and its heavy chain partner in the coiled coil. The invariant proline residues cause the heavy chains to flare to form the fork. The direction of the turn at the WQW sequence within the regulatory domain causes the long alpha-helix of the heavy chains within the head to continue the sense of the supercoil. With the bases of heads interacting, motion of the heads could still occur by a flexing of the coiled coil close to the heads and by a flexing and twisting of the long alpha-helices in the head. The model accounts for some of the conserved sequence features in myosins from different sources and provides a structural basis for understanding the head-head interactions in regulated myosin. Using the C alpha atoms of subfragment 1 we have also constructed a model with two complete heads. The clockwise curvature of the heads when the model is viewed end-on towards the tail accounts for the most common appearance of myosin molecules in electron micrographs. These models are predicated on the assumption that the entire heptad sequence of the heavy chains forms a coiled coil. Previous evidence from electron micrographs of myosin molecules that this was not the case can be explained by the foreshortening of the tail close to the heads.
通过将扇贝调节结构域连接到扇贝α-螺旋卷曲螺旋模型的两条α-螺旋链末端，构建了肌球蛋白分子头部与尾部连接处的原子模型。每个调节结构域重链的C末端α-螺旋与卷曲螺旋中的相应序列重叠。在构建的结构中，两个头部彼此相邻，基部相互接触，但明显没有空间冲突。两个头部之间的主要相互作用发生在调节轻链之间，并且在每个调节轻链与其在卷曲螺旋中的重链伙伴之间也存在头尾相互作用。不变的脯氨酸残基使重链展开形成叉状。调节结构域内WQW序列处的转角方向使头部内重链的长α-螺旋延续超螺旋的方向。由于头部基部相互作用，头部的运动仍可通过靠近头部的卷曲螺旋的弯曲以及头部中长α-螺旋的弯曲和扭转来实现。该模型解释了来自不同来源的肌球蛋白中一些保守的序列特征，并为理解调节型肌球蛋白中的头对头相互作用提供了结构基础。利用亚片段1的Cα原子，我们还构建了一个具有两个完整头部的模型。当从尾部端视该模型时，头部的顺时针弯曲解释了电子显微镜照片中肌球蛋白分子最常见的外观。这些模型基于重链的整个七肽序列形成卷曲螺旋的假设。先前从肌球蛋白分子电子显微镜照片得出的并非如此的证据，可以通过靠近头部的尾部缩短来解释。
