Hu Zhongjun, Taylor Dianne W, Edwards Robert J, Taylor Kenneth A
Florida State University, Institute of Molecular Biophysics, Tallahassee, FL 32306-4380, USA.
Duke University Medical Center, Department of Cell Biology, Durham, NC 27607, UK.
J Struct Biol. 2017 Dec;200(3):334-342. doi: 10.1016/j.jsb.2017.09.009. Epub 2017 Sep 28.
The recent high-resolution structure of the thick filament from Lethocerus asynchronous flight muscle shows aspects of thick filament structure never before revealed that may shed some light on how striated muscles function. The phenomenon of stretch activation underlies the function of asynchronous flight muscle. It is most highly developed in flight muscle, but is also observed in other striated muscles such as cardiac muscle. Although stretch activation is likely to be complex, involving more than a single structural aspect of striated muscle, the thick filament itself, would be a prime site for regulatory function because it must bear all of the tension produced by both its associated myosin motors and any externally applied force. Here we show the first structural evidence that the arrangement of myosin heads within the interacting heads motif is coupled to the structure of the thick filament backbone. We find that a change in helical angle of 0.16° disorders the blocked head preferentially within the Lethocerus interacting heads motif. This observation suggests a mechanism for how tension affects the dynamics of the myosin heads leading to a detailed hypothesis for stretch activation and shortening deactivation, in which the blocked head preferentially binds the thin filament followed by the free head when force production occurs.
巨水黾异步飞行肌肉粗肌丝的最新高分辨率结构揭示了粗肌丝结构中一些前所未有的方面，这可能有助于阐明横纹肌的功能机制。拉伸激活现象是异步飞行肌肉功能的基础。它在飞行肌肉中最为发达，但在其他横纹肌如心肌中也有观察到。尽管拉伸激活可能很复杂，涉及横纹肌的多个结构方面，但粗肌丝本身可能是调节功能的主要部位，因为它必须承受其相关肌球蛋白马达产生的所有张力以及任何外部施加的力。在这里，我们展示了首个结构证据，即相互作用头部基序内肌球蛋白头部的排列与粗肌丝主干的结构相关联。我们发现，螺旋角0.16°的变化会优先扰乱巨水黾相互作用头部基序内的受阻头部。这一观察结果提示了一种张力如何影响肌球蛋白头部动力学的机制，从而得出了关于拉伸激活和缩短失活的详细假设，即在产生力时，受阻头部优先结合细肌丝，随后是自由头部。
