Tugarinov Vitali, Torricella Francesco, Ghosh Shreya, Clore G Marius
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA.
Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-0520, USA.
J Mol Biol. 2025 Jun 9:169269. doi: 10.1016/j.jmb.2025.169269.
We provide an overview of the practical aspects of using NMR spectroscopy to follow the time course of protein fibril formation (aggregation) and quantitatively model the kinetics of aggregation processes. Following a brief survey of the theoretical foundations of the kinetics of protein aggregation and its inhibition, the modeling of aggregation kinetics, from data acquired by a series of fast two-dimensional H-N correlation NMR spectra, is described. Examples are drawn from our recent NMR-based studies of (1) the aggregation kinetics of a pathogenic huntingtin exon-1 protein whose fibrillization in neurons is responsible for Huntington's disease, and (2) the kinetics of amyloid β42 fibril formation and the mechanism of its inhibition by the chaperone Hsp104.
我们概述了使用核磁共振波谱法追踪蛋白质纤维形成（聚集）的时间进程并对聚集过程动力学进行定量建模的实际操作。在简要综述蛋白质聚集动力学及其抑制的理论基础之后，描述了如何根据一系列快速二维氢-氮相关核磁共振波谱获取的数据对聚集动力学进行建模。实例取自我们最近基于核磁共振的研究，包括：（1）致病性亨廷顿蛋白外显子1的聚集动力学，其在神经元中的纤维化是导致亨廷顿舞蹈病的原因；（2）淀粉样β42纤维形成的动力学及其被伴侣蛋白Hsp104抑制的机制。
