Lorenz M, Poole K J, Popp D, Rosenbaum G, Holmes K C
Max-Planck Institut für medizinische Forschung Abteilung Biophysik, Heidelberg, Germany.
J Mol Biol. 1995 Feb 10;246(1):108-19. doi: 10.1006/jmbi.1994.0070.
We present a model of the actin-tropomyosin complex in which the radial and azimuthal position of tropomyosin was adjusted to fit the X-ray fiber diffraction patterns from oriented actin-tropomyosin gels at a resolution of 1/8 A-1. We used the recently published atomic F-actin model for the calculations. The atomic model of tropomyosin was obtained by model-building a coiled coiled-coil structure from the tropomyosin sequence. The resulting atomic model is strongly preferred and shows strong electrostatic interactions between charged side-chains of tropomyosin residues and actin residues in subdomain 3 and subdomain 4. Furthermore, calculations of enthalpies based upon electrostatic interactions indicate that there is a favored rotational position of the tropomyosin core at the calculated azimuthal and radial position given by the X-ray refinement. Rotations of the tropomyosin strand out of this position turn strongly attractive electrostatic interactions into repulsive forces. The resulting binding radius of 39 A and the determined azimuthal position of tropomyosin are in good agreement with electron microscopy reconstructions and neutron diffraction experiments. Furthermore, the calculated position of tropomyosin would still partly block the rigor interaction of myosin cross-bridges with actin, whereas it very likely allows undisturbed binding of the cross-bridges in a weak binding state.
我们提出了一种肌动蛋白 - 原肌球蛋白复合物模型，其中原肌球蛋白的径向和方位角位置经过调整，以符合来自取向的肌动蛋白 - 原肌球蛋白凝胶的X射线纤维衍射图谱，分辨率为1/8 Å⁻¹。我们使用最近发表的原子F - 肌动蛋白模型进行计算。原肌球蛋白的原子模型是通过根据原肌球蛋白序列构建卷曲螺旋结构获得的。所得的原子模型是非常理想的，并且显示出原肌球蛋白残基的带电侧链与亚结构域3和亚结构域4中的肌动蛋白残基之间存在强烈的静电相互作用。此外，基于静电相互作用的焓计算表明，在X射线精修给出的计算方位角和径向位置处，原肌球蛋白核心存在一个有利的旋转位置。原肌球蛋白链偏离此位置的旋转会将强烈的吸引静电相互作用转变为排斥力。所得的39 Å结合半径和确定的原肌球蛋白方位角位置与电子显微镜重建和中子衍射实验结果高度吻合。此外，计算得到的原肌球蛋白位置仍会部分阻断肌球蛋白横桥与肌动蛋白的强直相互作用，而很可能允许横桥在弱结合状态下不受干扰地结合。
