Concise Report
Revealing the Regulation Effect of Surface Charge at Aromatic Interface to Dynamic Conformational Changes of α-Synuclein at Early Aggregation Stage
Yuqi Zhang,
Lie Wu,
Xiue Jiang,
Yuqi Zhang
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022 China
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026 China
Search for more papers by this authorCorresponding Author
Lie Wu
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022 China
Research Center for Analytical Science, College of Chemistry, Nankai University, Tianjin, 300071 China
E-mail: [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Xiue Jiang
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022 China
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026 China
Research Center for Analytical Science, College of Chemistry, Nankai University, Tianjin, 300071 China
E-mail: [email protected]; [email protected]Search for more papers by this authorYuqi Zhang,
Lie Wu,
Xiue Jiang,
Yuqi Zhang
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022 China
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026 China
Search for more papers by this authorCorresponding Author
Lie Wu
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022 China
Research Center for Analytical Science, College of Chemistry, Nankai University, Tianjin, 300071 China
E-mail: [email protected]; [email protected]Search for more papers by this authorCorresponding Author
Xiue Jiang
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022 China
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei, Anhui, 230026 China
Research Center for Analytical Science, College of Chemistry, Nankai University, Tianjin, 300071 China
E-mail: [email protected]; [email protected]Search for more papers by this authorFirst published: 24 April 2024
Comprehensive Summary
The aggregation of α-synuclein (α-syn) is strongly influenced by membrane interfaces, but the mechanism of transition from monomers to oligomers at early aggregation stage is not clear. Here, we investigate the adsorption and structure changes of α-syn on oppositely charged aromatic interfaces through in-situ surface-enhanced infrared absorption (SEIRA) spectroscopy and nano-IR technique. The results show that the synergy of electrostatic and hydrophobic interactions leads to a “fast-slow” two-step aggregation pathway on negatively charged interface. Surface 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 regions. Stable 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 exposure. Our 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 of α-syn at early aggregation stage and imply the important role of spatial-temporal heterogeneity of membranes in α-synucleinopathies.
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