Shannon Matthew D, Theint Theint, Mukhopadhyay Dwaipayan, Surewicz Krystyna, Surewicz Witold K, Marion Dominique, Schanda Paul, Jaroniec Christopher P
Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio, 43210, United States.
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, Ohio, 44106, United States.
Chemphyschem. 2019 Jan 21;20(2):311-317. doi: 10.1002/cphc.201800779. Epub 2018 Nov 7.
Microsecond to millisecond timescale backbone dynamics of the amyloid core residues in Y145Stop human prion protein (PrP) fibrils were investigated by using N rotating frame (R ) relaxation dispersion solid-state nuclear magnetic resonance spectroscopy over a wide range of spin-lock fields. Numerical simulations enabled the experimental relaxation dispersion profiles for most of the fibril core residues to be modelled by using a two-state exchange process with a common exchange rate of 1000 s , corresponding to protein backbone motion on the timescale of 1 ms, and an excited-state population of 2 %. We also found that the relaxation dispersion profiles for several amino acids positioned near the edges of the most structured regions of the amyloid core were better modelled by assuming somewhat higher excited-state populations (∼5-15 %) and faster exchange rate constants, corresponding to protein backbone motions on the timescale of ∼100-300 μs. The slow backbone dynamics of the core residues were evaluated in the context of the structural model of human Y145Stop PrP amyloid.
通过在广泛的自旋锁定场范围内使用N旋转框架（R）弛豫分散固态核磁共振光谱，研究了Y145Stop人朊病毒蛋白（PrP）纤维中淀粉样核心残基的微秒到毫秒时间尺度的主链动力学。数值模拟使得大多数纤维核心残基的实验弛豫分散谱能够通过一个双态交换过程进行建模，该过程具有1000 s的共同交换速率，对应于1 ms时间尺度上的蛋白质主链运动，以及2%的激发态丰度。我们还发现，对于位于淀粉样核心最结构化区域边缘附近的几个氨基酸，通过假设略高的激发态丰度（约5 - 15%）和更快的交换速率常数来更好地模拟弛豫分散谱，这对应于约100 - 300 μs时间尺度上的蛋白质主链运动。在人Y145Stop PrP淀粉样结构模型的背景下评估了核心残基的缓慢主链动力学。
