Université de Lyon, Institut de Sciences Analytiques (CNRS/ENS-Lyon/UCB-Lyon 1), Centre de Résonance Magnétique Nucléaire à Très Hauts Champs, 69100 Villeurbanne, France.
Université Grenoble Alpes, Institut de Biologie Structurale (IBS), F-38044 Grenoble, France; CNRS, IBS, F-38044 Grenoble, France; CEA, IBS, F-38044 Grenoble, France.
Science. 2015 May 1;348(6234):578-81. doi: 10.1126/science.aaa6111.
One of the fundamental challenges of physical biology is to understand the relationship between protein dynamics and function. At physiological temperatures, functional motions arise from the complex interplay of thermal motions of proteins and their environments. Here, we determine the hierarchy in the protein conformational energy landscape that underlies these motions, based on a series of temperature-dependent magic-angle spinning multinuclear nuclear-magnetic-resonance relaxation measurements in a hydrated nanocrystalline protein. The results support strong coupling between protein and solvent dynamics above 160 kelvin, with fast solvent motions, slow protein side-chain motions, and fast protein backbone motions being activated consecutively. Low activation energy, small-amplitude local motions dominate at low temperatures, with larger-amplitude, anisotropic, and functionally relevant motions involving entire peptide units becoming dominant at temperatures above 220 kelvin.
物理生物学的基本挑战之一是理解蛋白质动力学与功能之间的关系。在生理温度下，功能运动源于蛋白质及其环境的热运动的复杂相互作用。在这里，我们基于一系列水合纳米晶体蛋白质的依赖于温度的魔角旋转多核核磁共振弛豫测量，确定了这些运动所基于的蛋白质构象能量景观中的层次结构。结果表明，在 160 开尔文以上，蛋白质和溶剂动力学之间存在强耦合，快速溶剂运动、缓慢的蛋白质侧链运动和快速的蛋白质骨架运动依次被激活。在低温下，低激活能、小振幅局部运动占主导地位，而在 220 开尔文以上的温度下，涉及整个肽单元的更大振幅、各向异性和功能相关的运动成为主导。
