Graduate Group in Biochemistry and Molecular Biophysics, Department of Biochemistry & Biophysics, University of Pennsylvania, Philadelphia, 19104, United States.
J Am Chem Soc. 2012 May 23;134(20):8543-50. doi: 10.1021/ja3004655. Epub 2012 Apr 10.
The cooperative nature of protein substructure and internal motion is a critical aspect of their functional competence about which little is known experimentally. NMR relaxation is used here to monitor the effects of high pressure on fast internal motion in the protein ubiquitin. In contrast to the main chain, the motions of the methyl-bearing side chains have a large and variable pressure dependence. Within the core, this pressure sensitivity correlates with the magnitude of motion at ambient pressure. Spatial clustering of the dynamic response to applied hydrostatic pressure is also seen, indicating localized cooperativity of motion on the sub-nanosecond time scale and suggesting regions of variable compressibility. These and other features indicate that the native ensemble contains a significant fraction of members with characteristics ascribed to the recently postulated "dry molten globule". The accompanying variable side-chain conformational entropy helps complete our view of the thermodynamic architecture underlying protein stability, folding, and function.
蛋白质亚结构和内部运动的协同性是其功能能力的一个关键方面，但在实验上对此知之甚少。在这里，我们使用 NMR 弛豫来监测高压对蛋白质泛素中快速内部运动的影响。与主链不同，带甲基侧链的运动具有大的且可变的压力依赖性。在核心内，这种压力敏感性与环境压力下的运动幅度相关。对静水压力施加的动态响应的空间聚类也可见，表明在亚纳秒时间尺度上运动的局部协同性，并暗示了可变压缩性的区域。这些和其他特征表明，天然整体中包含有很大一部分具有最近提出的“干燥的无规卷曲”特性的成员。伴随的可变侧链构象熵有助于我们全面了解蛋白质稳定性、折叠和功能的热力学结构。
