Revealing the Regulation Effect of Surface Charge at Aromatic Interface to Dynamic Conformational Changes of α-Synuclein at Early Aggregation Stage

作     者：Yuqi Zhang Lie Wu Xiue Jiang Yuqi Zhang;Lie Wu;Xiue Jiang

作者机构：State Key Laboratoryof Electroanalytical ChemistryChangchun Institute of Applied ChemistryChinese Academy of SciencesChangchun Jilin 130022China Schoolof Applied Chemistry and EngineeringUniversity of Science and Technology of ChinaHefei Anhui 230026China Research Center for Analytical ScienceCollege of ChemistryNankai UniversityTianjin 300071China 

出 版 物：《Chinese Journal of Chemistry》 (中国化学（英文版）)

年 卷 期：2024年第42卷第16期

页      面：1867-1876页

核心收录：

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070305[理学-高分子化学与物理] 080501[工学-材料物理与化学] 0805[工学-材料科学与工程（可授工学、理学学位）] 0703[理学-化学] 

基　　金：financial support from National Key R&D Program of China(2022YFE0113000) the National Natural Science Foundation of China(22074138,22374083) the National Science Fund for Distinguished Young Scholars(22025406) Youth Innovation Promotion Association of CAs(Grant No.2020233) 

主　　题：α-Synuclein Interface Early aggregation IR spectroscopy Surface analysis Analytical methods Proteins Dynamic monitoring 

摘      要：The aggregation ofα-synuclein(α-syn)is strongly influenced by membrane interfaces,but the mechanism of transition from monomers to oligomers at early aggregation stage is not ***,we investigate the adsorption and structure changes ofα-syn on oppositely charged aromatic interfaces through in-situ surface-enhanced infrared absorption(SEIRA)spectroscopy and nano-IR *** results show that the synergy of electrostatic and hydrophobic interactions leads to a“fast-slowtwo-step aggregation pathway on negatively charged *** adsorption induces the formation of an extended helix structure and subsequently partial helix unwinding in NAC region,which enables the hydrophobic stacking between nearby NAC *** antiparallel β-sheet rich aggregates are gradually emerging as further interactions of monomers with the fast formed“first layer.Monomers electrostatically adsorb on positively charged interface by C-terminus with NAC region and N-terminus stretched in solvent,which serve as an aggregation core and induce further adsorption and gradual formation of aggregates with C-terminus *** results demonstrate the modulation of surface charge and synergy of electrostatic and hydrophobic interactions on the interaction modes and aggregation pathways,which provide insights into dynamic conformation changes ofα-syn at early aggregation stage and imply the important role of spatial-temporal heterogeneity of membranes inα-synucleinopathies.