Reedy M C, Beall C, Fyrberg E
Department of Cell Biology, Duke University Medical Center, Durham, North Carolina 27710.
Nature. 1989 Jun 8;339(6224):481-3. doi: 10.1038/339481a0.
The uniform angle and conformation of myosin subfragment 1 (S1) bound to actin filaments (F-actin) attest to the precise alignment and stereospecificity of the binding of these two contractile proteins. Because actin filaments are polar, myosin heads must swing or rotate about the head-tail junction in order to bind. Electron microscopy of isolated thick filaments and of myosin molecules suggests that the molecules are flexible, but myosin fragments and crossbridges have been reported not to interact with inappropriately oriented actin filaments. Here we describe myofibrillar defects engendered by a site-directed mutation within the flight-muscle-specific actin gene of the fruitfly Drosophila. The mutation apparently retards sarcomere assembly: peripheral thick and thin filaments are misregistered and not incorporated into the Z-line. Therefore, a myosin filament encounters thin filaments with the 'wrong' polarity. We show that myosin heads tethered in a single thick filament can bind with opposite rigor crossbridge angles to flanking thin filaments, which are apparently of opposite polarities. Preservation of identical actomyosin interfaces requires that sets of heads originating from opposite sides of the thick filament swivel 180 degrees relative to each other, implying that myosin crossbridges are as flexible as isolated molecules.
与肌动蛋白丝(F-肌动蛋白)结合的肌球蛋白亚片段1(S1)具有一致的角度和构象,这证明了这两种收缩蛋白结合时的精确排列和立体特异性。由于肌动蛋白丝是极性的,肌球蛋白头部必须围绕头尾连接处摆动或旋转才能结合。对分离出的粗肌丝和肌球蛋白分子进行的电子显微镜观察表明,这些分子是灵活的,但据报道,肌球蛋白片段和横桥不会与方向不当的肌动蛋白丝相互作用。在这里,我们描述了果蝇飞行肌特异性肌动蛋白基因中一个定点突变导致的肌原纤维缺陷。该突变显然会延迟肌节组装:外周的粗肌丝和细肌丝排列错误,没有并入Z线。因此,肌球蛋白丝会遇到极性“错误”的细肌丝。我们发现,束缚在单根粗肌丝中的肌球蛋白头部可以以相反的强直横桥角度与两侧的细肌丝结合,而两侧的细肌丝显然具有相反的极性。要保持相同的肌动球蛋白界面,就要求源自粗肌丝两侧的头部组相对于彼此旋转180度,这意味着肌球蛋白横桥与分离的分子一样灵活。