Department of Applied Bioscience, CHA University, Gyeonggi-do 463-863, Republic of Korea.
Colloids Surf B Biointerfaces. 2013 Jan 1;101:266-71. doi: 10.1016/j.colsurfb.2012.06.014. Epub 2012 Jun 29.
The misfolding and intracellular aggregation of Cu-Zn superoxide dismutase (SOD1) is pathologically key feature of amyotrophic lateral sclerosis (ALS). Although details of the mechanisms continue to be unclear, there are key steps in the possible pathway to the development of ALS. This study focuses on interactions between different SOD1 molecules (A4V apo/holo, and WT apo/holo) and homogeneous aggregates in the temporal evolution step, and a determination of whether any of the SOD1 molecules are reactive to the aggregates with the extent of binding, as determined by surface plasmon resonance (SPR) measurements. Using a kinetic binding model, the association constant of A4V apo was found to be three times larger than that for the WT apo species. Differences in the extent of the interactions were also simultaneously measured and visualized by means of SPR imaging techniques. The SPR-based approach suggests direct correlation between SPR signal and the extent of molecular binding, which can identify the significant contributors to the formation of macroaggregates of SOD1 in the temporal evolution step.
铜锌超氧化物歧化酶（SOD1）的错误折叠和细胞内聚集是肌萎缩侧索硬化症（ALS）的病理关键特征。尽管其机制的细节仍不清楚，但 ALS 发展的可能途径中有几个关键步骤。本研究集中于在时间演化步骤中不同 SOD1 分子（A4V 脱辅基/全酶和 WT 脱辅基/全酶）与均一聚集体之间的相互作用，并确定任何 SOD1 分子是否与聚集体发生反应以及结合的程度，通过表面等离子体共振（SPR）测量来确定。使用动力学结合模型，发现 A4V 脱辅基的缔合常数比 WT 脱辅基的大三倍。通过 SPR 成像技术，还同时测量和可视化了相互作用程度的差异。基于 SPR 的方法表明 SPR 信号与分子结合程度之间存在直接相关性，这可以确定在时间演化步骤中 SOD1 宏观聚集体形成的重要贡献者。
