文献类型：期刊文献

英文题名：Snapshotting the transient conformations and tracing the multiple pathways of single peptide folding using a solid-state nanopore

作者：Liu, Shao-Chuang[1,2];Ying, Yi-Lun[1,2];Li, Wei-Hua[3];Wan, Yong-Jing[4];Long, Yi-Tao[1,2]

机构：[1]Nanjing Univ, State Key Lab Analyt Chem Life Sci, Sch Chem & Chem Engn, Nanjing 210023, Peoples R China;[2]East China Univ Sci & Technol, Dept Chem, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China;[4]East China Univ Sci & Technol, Sch Informat Sci & Engn, Shanghai 200237, Peoples R China

年份：2021

卷号：12

期号：9

起止页码：3282

外文期刊名：CHEMICAL SCIENCE

收录：;EI(收录号：20211110086444);WOS:【SCI-EXPANDED(收录号:WOS:000627505700020)】；

基金：This research was supported by the National Natural Science Foundation of China (22027806, 22090051 and 21922405), the Excellent Research Program of Nanjing University (ZYJH004), and the Fundamental Research Funds for the Central Universities (14380239). S. C. L. is supported by the Open Research Fund of State Key Laboratory of Bioelectronics, Southeast University. We thank Ms Huiying Li for help with Native-PAGE experiments.

语种：英文

外文关键词：Peptides - Protein folding - Markov processes - Nanopores

摘要：A fundamental question relating to protein folding/unfolding is the time evolution of the folding of a protein into its precisely defined native structure. The proper identification of transition conformations is essential for accurately describing the dynamic protein folding/unfolding pathways. Owing to the rapid transitions and sub-nm conformation differences involved, the acquisition of the transient conformations and dynamics of proteins is difficult due to limited instrumental resolution. Using the electrochemical confinement effect of a solid-state nanopore, we were able to snapshot the transient conformations and trace the multiple transition pathways of a single peptide inside a nanopore. By combining the results with a Markov chain model, this new single-molecule technique is applied to clarify the transition pathways of the beta-hairpin peptide, which shows nonequilibrium fluctuations among several blockage current stages. This method enables the high-throughput investigation of transition pathways experimentally to access previously obscure peptide dynamics, which is significant for understanding the folding/unfolding mechanisms and misfolding of peptides or proteins.