A mixed-kinetic model describes unloaded velocities of smooth, skeletal, and cardiac muscle myosin filaments in vitro.
A mixed-kinetic model describes unloaded velocities of smooth, skeletal, and cardiac muscle myosin filaments in vitro.
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DOI：
10.1126/sciadv.aao2267
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发表时间：
2017-12
期刊：
影响因子：
13.6
通讯作者：
Cremo CR
中科院分区：
文献类型：
--
作者：
Brizendine RK;Sheehy GG;Alcala DB;Novenschi SI;Baker JE;Cremo CR
重组类肌肉实验揭示了控制肌肉收缩速度的新机制。体外运动测定，纯化的肌凝蛋白和肌动蛋白彼此相对运动，用于更好地理解肌动球蛋白腺苷三磷酸酶（ATPase）循环的机械化学。我们研究了肌动蛋白和肌凝蛋白的相对速度(V)与平滑（SMM）、骨骼（SKM）和心脏（CMM）肌凝蛋白丝在肌动蛋白上移动的可用肌凝蛋白头(N)或[ATP]的数量之间的关系，以及肌动蛋白丝在单体SKM床上移动的V之间的关系。这些数据并不符合一个被广泛接受的模型，该模型预测V受到肌凝蛋白与肌动蛋白分离（d/ton）的限制，其中d等于步长，而ton等于肌凝蛋白头部附着在肌动蛋白上的时间。为了解释这些数据，我们开发了一个混合动力学模型，其中V受到附着和脱离动力学的影响。在给定的V下，相对贡献随头部附着在肌动蛋白上的时间足够长，达到其柔性S2系链末端的概率而变化。剥离动力学受L/ton的影响，其中L与系绳长度有关。我们发现SMM、SKM和CMM长丝的L相对较长（分别为59±3 nm、22±9 nm和22±2 nm）。相反，当肌球蛋白单体附着在表面时，L较短（8±3 nm）。这表明S2结构域的行为可能是肌凝蛋白细丝的一个重要的机械特征，它影响肌肉的空载缩短速度。
Reconstituted muscle-like assays reveal novel mechanisms that control the speed of muscle contraction. In vitro motility assays, where purified myosin and actin move relative to one another, are used to better understand the mechanochemistry of the actomyosin adenosine triphosphatase (ATPase) cycle. We examined the relationship between the relative velocity (V) of actin and myosin and the number of available myosin heads (N) or [ATP] for smooth (SMM), skeletal (SKM), and cardiac (CMM) muscle myosin filaments moving over actin as well as V from actin filaments moving over a bed of monomeric SKM. These data do not fit well to a widely accepted model that predicts that V is limited by myosin detachment from actin (d/ton), where d equals step size and ton equals time a myosin head remains attached to actin. To account for these data, we have developed a mixed-kinetic model where V is influenced by both attachment and detachment kinetics. The relative contributions at a given V vary with the probability that a head will remain attached to actin long enough to reach the end of its flexible S2 tether. Detachment kinetics are affected by L/ton, where L is related to the tether length. We show that L is relatively long for SMM, SKM, and CMM filaments (59 ± 3 nm, 22 ± 9 nm, and 22 ± 2 nm, respectively). In contrast, L is shorter (8 ± 3 nm) when myosin monomers are attached to a surface. This suggests that the behavior of the S2 domain may be an important mechanical feature of myosin filaments that influences unloaded shortening velocities of muscle.
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影响因子：
13.6
作者：
Kawana M;Sarkar SS;Sutton S;Ruppel KM;Spudich JA
通讯作者：
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作者：
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