State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, National Center for Magnetic Resonance in Wuhan, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan, China.
University of Chinese Academy of Sciences, Beijing, China.
Biomol NMR Assign. 2022 Oct;16(2):187-190. doi: 10.1007/s12104-022-10077-4. Epub 2022 Jun 17.
Abnormal protein aggregation and precipitation are associated with the perturbation of cellular function and underlie a variety of neurodegenerative diseases. S. cerevisiae SERF (ScSERF), a homolog of modifier of aggregation-4 (MOAG-4) and small EDRK-rich factor protein (SERF1a) is highly conserved and discovered as an enhancer of amyloid formation of Aβ40 and α-synuclein both in vitro and in vivo. However, the detailed molecular mechanism whereby ScSERF and its homologs accelerate amyloid formation is not well known yet. Herein, we present the H, N and C NMR assignments of the 68 amino acids long ScSERF. Although ScSERF displays a very high degree of disorder, secondary chemical shifts of C, C, N{ H}-NOE values and the residue-specific secondary structure propensity (SSP) scores indicate the segment spanning residues 36E-65 K has a strong helical propensity. This work sets the stage for further detailed structural and dynamic investigations of ScSERF and the molecular mechanism it utilizes in accelerating amyloid formation.
异常蛋白聚集和沉淀与细胞功能的紊乱有关，是多种神经退行性疾病的基础。酿酒酵母 SERF（ScSERF）是修饰聚集物-4（MOAG-4）和小 EDRK 丰富因子蛋白（SERF1a）的同源物，高度保守，在体外和体内均被发现可增强 Aβ40 和 α-突触核蛋白的淀粉样形成。然而，ScSERF 及其同源物加速淀粉样形成的详细分子机制尚不清楚。在此，我们给出了 68 个氨基酸长的 ScSERF 的 H、N 和 C NMR 分配。尽管 ScSERF 表现出非常高的无序度，但 C、C、N{ H}-NOE 值的二级化学位移和残基特异性二级结构倾向（SSP）分数表明，残基 36E-65 K 跨越的片段具有很强的螺旋倾向。这项工作为进一步详细研究 ScSERF 的结构和动力学以及它在加速淀粉样形成中所利用的分子机制奠定了基础。
