Department of Immunology, Binzhou Medical University, Yantai, 264003, P. R. China.
State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, National Center for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Hubei, 430071, P. R. China.
Chemistry. 2023 May 26;29(30):e202203965. doi: 10.1002/chem.202203965. Epub 2023 Apr 20.
The aggregation of amyloidogenic proteins is often related to the occurrence of neurodegenerative diseases, including fused in sarcoma protein (FUS) in frontotemporal lobar degeneration and amyotrophic lateral sclerosis diseases. Recently, the SERF protein family has been reported to have a significant regulatory effect on amyloid formation, but it is still unclear about the detailed mechanisms of SERF acting on different amyloidogenic proteins. Herein, nuclear magnetic resonance (NMR) spectroscopy and fluorescence spectroscopy were used to explore interactions of ScSERF with three amyloidogenic proteins FUS-LC, FUS-Core, and α-Synuclein. NMR chemical shift perturbations reveal them sharing similar interaction sites on the N-terminal region of ScSERF. However, the amyloid formation of α-Synuclein protein is accelerated by ScSERF, while ScSERF inhibits fibrosis of FUS-Core and FUS-LC proteins. Both the primary nucleation and the total amount of fibrils produced are detained. Our results suggest a diverse role of ScSERF in regulating the fibril growth of amyloidogenic proteins.
淀粉样蛋白的聚集通常与神经退行性疾病的发生有关，包括融合肉瘤蛋白（FUS）在前额颞叶变性和肌萎缩侧索硬化症中的作用。最近，SERF 蛋白家族被报道对淀粉样形成有显著的调节作用，但关于 SERF 对不同淀粉样蛋白的作用的详细机制仍不清楚。在这里，我们使用核磁共振（NMR）光谱和荧光光谱来研究 ScSERF 与三种淀粉样蛋白 FUS-LC、FUS-Core 和 α-突触核蛋白的相互作用。NMR 化学位移扰动表明它们在 ScSERF 的 N 端区域共享相似的相互作用位点。然而，ScSERF 加速了 α-突触核蛋白的淀粉样形成，而 ScSERF 抑制了 FUS-Core 和 FUS-LC 蛋白的纤维化。原纤维的成核和总生成量都被阻滞。我们的结果表明 ScSERF 在调节淀粉样蛋白的纤维生长中具有多样化的作用。
