Actin fliament plasys an impoilant paIl as to the myosin motility mechanism

我们已经证明了具有非常短的颈域的肌球蛋白-V的截断突变体(Tanaka等人‘02)和肌球蛋白-VI的截断突变体(Nishikawa等人’02)发育出与具有长颈域的天然肌球蛋白-V一样大的连续步骤。在这里，我们提出了一个可能的模型(应变传感器模型)来解释这些结果，而不是杠杆臂模型。当头部在弹簧的热弯曲和拉伸的驱动下向前移动到靶区并与肌动蛋白结合时，传感器被拉动和应变，以允许运动域与肌动蛋白强烈结合，这可能与磷酸盐的释放或肌球蛋白的异构化有关。当电机磁区在相反方向上热扩散时，应变传感器不工作，因为应变方向相反，磁头返回到原始位置。同时，EM图像显示，在ATP存在的情况下，肌球蛋白VI以36 nm的间隔(热点)协同结合到肌动蛋白细丝上。此外，我们还利用单分子成像技术得到了肌球蛋白促进肌动蛋白细丝正向结合的结果。肌球蛋白头部和肌动蛋白之间的界面上的肌球蛋白同种类型的特定相互作用将决定向邻近的“热点”移动的方向，这种相互作用造成了布朗运动的偏差。靶纤维的构象变化也应该在肌球蛋白的进行性运动中发挥重要作用。

We have shown that a truncation mutant of myosin-V (Tanaka et al.'02) and myosin-VI (Nishikawa et al.'02) with very short neck domains develop successive steps as large as native myosin-V with long neck domains. Here, we propose a possible model (strain-sensor model) to explain these results, instead of the lever arm model. When the head moves to the target zone in the forward direction, driven by thermal bending and stretching of the spring and binds to actin, the sensor is pulled and strained to allow the motor domain to bind strongly to the actin, probably coupled to the release of phosphate or the isomerization of myosin. When the motor domain thermally diffuses in the opposite direction, the strain-sensor does not operate because the direction of strain is opposite and the head returns to the original position. Thus, the myosin head favorably moves to the next target in the forward direction.In the meantime, EM image showed that myosin VI cooperatively binds to an actin filament at 36nm intervals ("hot spot") in the presence of ATP. Furthermore, we also obtained the result of which the myosin facilitates the combination on actin filament forward direction using single molecule imaging. The direction of the movement to the neighboring "hot spot" would be determined by the myosin isotype specific interaction at the interface between myosin head and actin that creates a bias on the Brownian motion. Conformational changes in aim filaments should also play an important role in myosin processive moving.