Department of Chemistry and Biomedical Sciences, Linnaeus University, Universitetskajen, 391 82 Kalmar, Sweden.
Int J Mol Sci. 2020 Nov 9;21(21):8399. doi: 10.3390/ijms21218399.
Muscle contraction results from cyclic interactions between myosin II motors and actin with two sets of proteins organized in overlapping thick and thin filaments, respectively, in a nearly crystalline lattice in a muscle sarcomere. However, a sarcomere contains a huge number of other proteins, some with important roles in muscle contraction. In particular, these include thin filament proteins, troponin and tropomyosin; thick filament proteins, myosin binding protein C; and the elastic protein, titin, that connects the thin and thick filaments. Furthermore, the order and 3D organization of the myofilament lattice may be important per se for contractile function. It is possible to model muscle contraction based on actin and myosin alone with properties derived in studies using single molecules and biochemical solution kinetics. It is also possible to reproduce several features of muscle contraction in experiments using only isolated actin and myosin, arguing against the importance of order and accessory proteins. Therefore, in this paper, it is hypothesized that "single molecule actomyosin properties account for the contractile properties of a half sarcomere during shortening and isometric contraction at almost saturating Ca concentrations". In this paper, existing evidence for and against this hypothesis is reviewed and new modeling results to support the arguments are presented. Finally, further experimental tests are proposed, which if they corroborate, at least approximately, the hypothesis, should significantly benefit future effective analysis of a range of experimental studies, as well as drug discovery efforts.
肌肉收缩是由肌球蛋白 II 马达与肌动蛋白之间的循环相互作用引起的，肌球蛋白 II 马达和肌动蛋白分别由两组蛋白质组成，在肌肉肌节中形成近乎结晶的晶格，这些蛋白质分别组织在重叠的粗丝和细丝中。然而，肌节中还包含大量其他蛋白质，其中一些在肌肉收缩中起着重要作用。特别是，这些蛋白质包括细丝蛋白、肌钙蛋白和原肌球蛋白；粗丝蛋白、肌球蛋白结合蛋白 C；以及连接细丝和粗丝的弹性蛋白，即肌联蛋白。此外，肌丝晶格的顺序和 3D 组织本身对于收缩功能可能很重要。仅基于肌动蛋白和肌球蛋白并利用使用单分子和生化溶液动力学研究中得出的特性，就可以对肌肉收缩进行建模。仅使用分离的肌动蛋白和肌球蛋白，也可以在实验中再现肌肉收缩的几个特征，这表明秩序和辅助蛋白的重要性不大。因此，在本文中，假设“单分子肌球蛋白的特性解释了在几乎饱和的 Ca 浓度下缩短和等长收缩期间半肌节的收缩特性”。本文回顾了支持和反对这一假设的现有证据，并提出了新的建模结果来支持这些论点。最后，提出了进一步的实验测试，如果这些实验测试至少近似地证实了该假设，那么它们应该会极大地有助于未来对一系列实验研究的有效分析，以及药物发现工作。
