Tropomyosin movement is described by a quantitative high-resolution model of X-ray diffraction of contracting muscle
Tropomyosin movement is described by a quantitative high-resolution model of X-ray diffraction of contracting muscle
复制标题
原肌球蛋白的运动通过收缩肌肉的 X 射线衍射的定量高分辨率模型来描述
DOI：
10.1007/s00249-016-1174-6
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
A. Tsaturyan
中科院分区：
文献类型：
--
作者：
N. Koubassova;S. Bershitsky;M. Ferenczi;T. Narayanan;A. Tsaturyan
骨骼肌和心肌的收缩受钙离子通过调节蛋白、肌钙蛋白（Tn）和原肌球蛋白（Tpm）控制，这些蛋白与肌节中的细肌动蛋白丝相关。在没有钙离子时，Tn - C结合肌动蛋白并使Tpm链移动到一个位置，在此位置它阻止肌球蛋白与肌动蛋白结合，使肌肉保持松弛。根据三态模型（McKillop和Geeves，《生物物理学杂志》65:693 - 701，1993），当钙离子与Tn结合时，Tpm围绕丝轴旋转到一个“关闭状态”，此时一些肌球蛋白头部可以结合肌动蛋白。当肌球蛋白头部与肌动蛋白强结合时，Tpm进一步旋转到一个“开放”位置，在此位置相邻的肌动蛋白单体也可用于肌球蛋白结合。收缩肌肉中Tpm的方位移动通过小角度X射线衍射检测。在此，我们基于近期的冷冻电镜数据使用肌动蛋白 - Tpm丝的高分辨率模型，以计算调节系统不同状态之间转换时肌肉X射线衍射反射强度的变化。计算得到的肌动蛋白层线强度与从处于松弛和僵直状态的兔肌肉纤维获得的实验数据的拟合度，比之前低分辨率模型有了很大提高。我们表明，在倒易半径从0.15到0.3 nm⁻¹范围内的第二肌动蛋白层线强度定量地反映了调节系统不同状态之间的转换，而与结合到肌动蛋白上的肌球蛋白头部数量无关。
Contraction of skeletal and cardiac muscle is controlled by Ca2+ ions via regulatory proteins, troponin (Tn) and tropomyosin (Tpm) associated with the thin actin filaments in sarcomeres. In the absence of Ca2+, Tn-C binds actin and shifts the Tpm strand to a position where it blocks myosin binding to actin, keeping muscle relaxed. According to the three-state model (McKillop and Geeves Biophys J 65:693–701, 1993), upon Ca2+ binding to Tn, Tpm rotates about the filament axis to a ‘closed state’ where some myosin heads can bind actin. Upon strong binding of myosin heads to actin, Tpm rotates further to an ‘open’ position where neighboring actin monomers also become available for myosin binding. Azimuthal Tpm movement in contracting muscle is detected by low-angle X-ray diffraction. Here we used high-resolution models of actin-Tpm filaments based on recent cryo-EM data for calculating changes in the intensities of X-ray diffraction reflections of muscle upon transitions between different states of the regulatory system. Calculated intensities of actin layer lines provide a much-improved fit to the experimental data obtained from rabbit muscle fibers in relaxed and rigor states than previous lower-resolution models. We show that the intensity of the second actin layer line at reciprocal radii from 0.15 to 0.3 nm−1 quantitatively reports the transition between different states of the regulatory system independently of the number of myosin heads bound to actin.
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影响因子：
64.8
作者：
von der Ecken, Julian;Mueller, Mirco;Lehman, William;Manstein, Dietmar J.;Penczek, Pawel A.;Raunser, Stefan
通讯作者：
Raunser, Stefan
影响因子：
3
作者：
Chen, LF;Winkler, H;Taylor, KA
通讯作者：
Taylor, KA
影响因子：
64.5
作者：
Behrmann E;Müller M;Penczek PA;Mannherz HG;Manstein DJ;Raunser S
通讯作者：
Raunser S
影响因子：
5.6
作者：
Vibert, P;Craig, R;Lehman, W
通讯作者：
Lehman, W