Department of Chemistry, University of Colorado Denver, Denver, CO, 80204, USA.
Solid State Nucl Magn Reson. 2021 Feb;111:101710. doi: 10.1016/j.ssnmr.2020.101710. Epub 2021 Jan 7.
Slow timescale dynamics in proteins are essential for a variety of biological functions spanning ligand binding, enzymatic catalysis, protein folding and misfolding regulations, as well as protein-protein and protein-nucleic acid interactions. In this review, we focus on the experimental and theoretical developments of H static NMR methods applicable for studies of microsecond to millisecond motional modes in proteins, particularly rotating frame relaxation dispersion (R), quadrupolar Carr-Purcell-Meiboom-Gill (QCPMG) relaxation dispersion, and quadrupolar chemical exchange saturation transfer NMR experiments (Q-CEST). With applications chosen from amyloid-β fibrils, we show the complementarity of these approaches for elucidating the complexities of conformational ensembles in disordered domains in the non-crystalline solid state, with the employment of selective deuterium labels. Combined with recent advances in relaxation dispersion backbone measurements for N/C/H nuclei, these techniques provide powerful tools for studies of biologically relevant timescale dynamics in disordered domains in the solid state.
蛋白质的慢时间尺度动力学对于各种生物学功能至关重要，包括配体结合、酶催化、蛋白质折叠和错误折叠调节，以及蛋白质-蛋白质和蛋白质-核酸相互作用。在这篇综述中，我们重点介绍了适用于研究蛋白质中微秒到毫秒运动模式的 H 静态 NMR 方法的实验和理论进展，特别是旋转框架弛豫分散（R）、四极 Carr-Purcell-Meiboom-Gill（QCPMG）弛豫分散和四极化学交换饱和转移 NMR 实验（Q-CEST）。我们选择了淀粉样β纤维作为应用实例，展示了这些方法在阐明非晶态固体中无定形域中构象集合体的复杂性方面的互补性，同时使用了选择性氘标记。结合最近在 N/C/H 核弛豫分散背底测量方面的进展，这些技术为研究无定形域中与生物学相关的时间尺度动力学提供了有力的工具。
