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ShanghaiTech University Knowledge Management System
| Single-molecule insight into α-synuclein fibril structure and mechanics modulated by chemical compounds | |
| 2025-02-14 | |
| 发表期刊 | ADVANCED SCIENCE (IF:14.3[JCR-2023],16.3[5-Year]) |
| ISSN | 2198-3844 |
| EISSN | 2198-3844 |
| 卷号 | 12页码:2416721 |
| 发表状态 | 已发表 |
| DOI | 10.1002/advs.202416721 |
| 摘要 | alpha-Syn fibrils, a key pathological hallmark of Parkinson's disease, is closely associated with disease initiation and progression. Several small molecules are found to bind or dissolve alpha-syn fibrils, offering potential therapeutic applications. Here, an innovative optical tweezers-based, fluorescence-combined approach is developed to probe the mechanical characteristics of alpha-syn fibrils at the single-molecule level. When subjected to axial stretching, local deformation within alpha-syn fibrils appeared at forces above 50 pN. These structural alternations occurred stepwise and are irreversible, suggesting unfolding of individual alpha-syn molecules or subdomains. Additionally, alpha-syn fibrils exhibits high heterogeneity in lateral disruption, with rupture force ranging from 50 to 500 pN. The impact of different compounds on the structure and mechanical features of alpha-syn fibrils is further examined. Notably, epigallocatechin gallate (EGCG) generally attenuates the rupture force of fibrils by wedging into the N-terminal polar groove and induces fibril dissociation. Conversely, copper chlorophyllin A (CCA) attaches to four different sites wrapping around the fibril core, reinforcing the stability of the fibril against rupture forces. The work offers an effective method for characterizing single-fibril properties and bridges compound-induced structural alternations with mechanical response. These insights are valuable for understanding amyloid fibril mechanics and their regulation by small molecules. |
| 关键词 | chemical compounds optical tweezers parkinson's disease single molecule alpha-synuclein fibril |
| URL | 查看原文 |
| 收录类别 | SCI ; EI |
| 语种 | 英语 |
| 资助项目 | Shanghai Pilot Program for Basic Research - Chinese Academy of Science, Shanghai Branch["82188101","22425704","32171236","32494764","92353302","32170683","32271505","32471508","32100993"] ; National Natural Science Foundation (NSF) of China["22JC1410400","22ZR1441900","23ZR1442200"] ; Science and Technology Commission of Shanghai Municipality (STCSM)["SLST-YS2024004","CYJ-SHFY-2022-005"] ; ShanghaiTech University School of Life Science and Technology Development Fund[095] ; Shanghai Basic Research Pioneer Project[XDB1060000] |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| WOS类目 | Chemistry, Multidisciplinary ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary |
| WOS记录号 | WOS:001421801100001 |
| 出版者 | WILEY |
| EI入藏号 | 20250917953144 |
| EI主题词 | Organometallics |
| EI分类号 | 802.2 Chemical Reactions ; 804.1 Organic Compounds |
| 原始文献类型 | Article in Press |
| 文献类型 | 期刊论文 |
| 条目标识符 | https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/484017 |
| 专题 | 生命科学与技术学院_PI研究组_孙博组 生命科学与技术学院_硕士生 生命科学与技术学院_博士生 |
| 共同第一作者 | Bi, Lulu |
| 通讯作者 | Sun, Bo; Liu, Cong |
| 作者单位 | 1.Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China 2.Zhangjiang Institute for Advanced Study, Shanghai Jiao Tong University, Shanghai 201203, China 3.School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China. 4.Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201210, China 5.University of the Chinese Academy of Sciences, Beijing 100049, China 6.Shanghai University of Medicine and Health Sciences Affiliated Zhoupu Hospital, Shanghai 201318, China 7.Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China 8.State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China |
| 通讯作者单位 | 生命科学与技术学院 |
| 推荐引用方式 GB/T 7714 | Li, Xiang,Bi, Lulu,Zhang, Shenqing,et al. Single-molecule insight into α-synuclein fibril structure and mechanics modulated by chemical compounds[J]. ADVANCED SCIENCE,2025,12:2416721. |
| APA | Li, Xiang.,Bi, Lulu.,Zhang, Shenqing.,Xu, Qianhui.,Xia, Wencheng.,...&Liu, Cong.(2025).Single-molecule insight into α-synuclein fibril structure and mechanics modulated by chemical compounds.ADVANCED SCIENCE,12,2416721. |
| MLA | Li, Xiang,et al."Single-molecule insight into α-synuclein fibril structure and mechanics modulated by chemical compounds".ADVANCED SCIENCE 12(2025):2416721. |
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