CIC nanoGUNE, San Sebastian, Spain.
Laboratory of Molecular Modeling, Federal University of São João del-Rei, São João del-Rei, Brazil.
Nat Struct Mol Biol. 2017 Aug;24(8):652-657. doi: 10.1038/nsmb.3426. Epub 2017 Jul 3.
The sarcomere-based structure of muscles is conserved among vertebrates; however, vertebrate muscle physiology is extremely diverse. A molecular explanation for this diversity and its evolution has not been proposed. We use phylogenetic analyses and single-molecule force spectroscopy (smFS) to investigate the mechanochemical evolution of titin, a giant protein responsible for the elasticity of muscle filaments. We resurrect eight-domain fragments of titin corresponding to the common ancestors to mammals, sauropsids, and tetrapods, which lived 105-356 Myr ago, and compare them with titin fragments from some of their modern descendants. We demonstrate that the resurrected titin molecules are rich in disulfide bonds and display high mechanical stability. These mechanochemical elements have changed over time, creating a paleomechanical trend that seems to correlate with animal body size, allowing us to estimate the sizes of extinct species. We hypothesize that mechanical adjustments in titin contributed to physiological changes that allowed the muscular development and diversity of modern tetrapods.
肌肉的肌节结构在脊椎动物中是保守的；然而，脊椎动物的肌肉生理学是极其多样化的。对于这种多样性及其进化，还没有提出分子解释。我们使用系统发育分析和单分子力谱（smFS）来研究肌联蛋白的机械化学进化，肌联蛋白是一种负责肌肉丝弹性的巨大蛋白。我们复活了对应于 1.05-3.56 亿年前哺乳动物、蜥形类和四足动物共同祖先的八结构域肌联蛋白片段，并将它们与一些现代后代的肌联蛋白片段进行比较。我们证明，复活的肌联蛋白分子富含二硫键，并且表现出很高的机械稳定性。这些机械化学元素随着时间的推移而发生变化，形成了一种古机械趋势，似乎与动物体型相关，使我们能够估计已灭绝物种的体型。我们假设，肌联蛋白的机械调整有助于生理变化，从而使现代四足动物的肌肉发育和多样性成为可能。
