Visible-Light-Controlled Lysine-Selective Crosslinking Decodes Protein Complexes and Dynamic Interactomes in Live Cells
文献类型：期刊论文
| 作者 | Xu, Yali7; Hu, Hao7; Ran, Yu6; Zhao, Wensi4,5; Guo, An-Di7; Nie, Hui-Jun7; Zhai, Linhui4,5; Yin, Guang-Liang3,7; Cheng, Jintao6; Tao, Shengna7 |
| 刊名 | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
 |
| 出版日期 | 2025-06-18 |
| 页码 | 15 |
| 关键词 | Chemoproteomics Molecular glue degraders Photo-crosslinking Protein-protein interactions Targeted protein degradation |
| DOI | 10.1002/anie.202507254 |
| 英文摘要 | Crosslinking strategies have emerged as an attractive technology for deciphering protein complexes and protein-protein interactions (PPIs). However, commonly used crosslinking strategies present significant challenges for the precise analysis of protein complexes and dynamic PPIs in native biological environments. Here, we report the development of the first visible-light-inducible lysine-specific homobifunctional photo-crosslinkers and introduce Visible-light-controlled Lysine-selective crosslinking (VL-XL) strategy for in-depth analysis of protein complexes and profiling dynamic interactomes in live cells. By synergistically integrating the advantages of temporal control, high biocompatibility, and lysine selectivity, the VL-XL strategy not only provides an effective solution for protein complexes studies-achieving residue-specific crosslinked peptides, delivering high-confidence data and streamlined mass spectrometry (MS) data analysis-but also reveals dynamic interactomes in various scenarios. The VL-XL strategy successfully profiles the time-resolved, epidermal growth factor (EGF)-stimulated epidermal growth factor receptor (EGFR) interactome, providing valuable insights into regulatory mechanisms of EGFR signaling. More importantly, the VL-XL strategy effectively unveils molecular glue degrader-induced E3 ligase interactome, leading to discovery of neo-substrates such as Sestrin-2 (SESN2) and opening an innovative avenue for identifying novel targets for degradation. Overall, the VL-XL strategy provides a robust chemical tool, inspiring innovative solutions to address unresolved questions in multiple fields. |
| WOS关键词 | MASS-SPECTROMETRY ; CYCLIZATION ; CAPTURE |
| 资助项目 | National Science Foundation of China ; Shanghai Institute of Materia Medica[SIMM0220233001] ; [22177120] ; [22307126] ; [22377133] ; [22374128] ; [22225702] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:001519267700001 |
| 出版者 | WILEY-V C H VERLAG GMBH |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/318705]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Yang, Bing; Tan, Minjia; Chen, Xiao-Hua |
| 作者单位 | 1.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Pharmaceut Sci & Technol, Hangzhou 310024, Peoples R China 2.Chinese Acad Sci, Zhongshan Inst Drug Discovery, Shanghai Inst Mat Med, Zhongshan 528400, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 4.Tongji Univ, Canc Ctr, Sch Med, Shanghai 200434, Peoples R China 5.Tongji Univ, Shanghai Peoples Hosp 4, Translat Res Inst Brain & Brain Like Intelligence, Shanghai 200434, Peoples R China 6.Zhejiang Univ, Life Sci Inst, Hangzhou 310058, Peoples R China 7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Xu, Yali,Hu, Hao,Ran, Yu,et al. Visible-Light-Controlled Lysine-Selective Crosslinking Decodes Protein Complexes and Dynamic Interactomes in Live Cells[J]. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,2025:15. |
| APA | Xu, Yali.,Hu, Hao.,Ran, Yu.,Zhao, Wensi.,Guo, An-Di.,...&Chen, Xiao-Hua.(2025).Visible-Light-Controlled Lysine-Selective Crosslinking Decodes Protein Complexes and Dynamic Interactomes in Live Cells.ANGEWANDTE CHEMIE-INTERNATIONAL EDITION,15. |
| MLA | Xu, Yali,et al."Visible-Light-Controlled Lysine-Selective Crosslinking Decodes Protein Complexes and Dynamic Interactomes in Live Cells".ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2025):15. |
入库方式： OAI收割
来源：上海药物研究所
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