
医学创新论坛第91期
时间:2025年12月24日(周三)下午16:00
地点:首都医科大学基础科研楼北楼二层多功能厅
主持人:
姜汉杰
首都医学科学创新中心
报告人:
吴明轩
副教授
西湖大学理学院化学系
报告题目:
Development of sulfonium and diazonium tools to investigate lysine methylation
摘要:
Lysine methylation is a posttranslational modification (PTM) that regulates many cellular processes. For example, histone H3K27 methylation leads to gene silence as an important type of epigenetic marks. Hypermethylation of histone H3K27 may drive cancer and the methyltransferase EZH2 is a hot drug target. Therefore, understanding of lysine methylation function is important to both basic and translational research. My lab aims to develop new chemical tools to study proteins that are involved in lysine methylation and identify novel lysine methylation sites. First, we developed nucleosome probes and sulfonium probes that enable selective crosslinking to methyllysine readers. New readers including PWWP4 and BWRD3 were identified from cellular samples. Second, we developed aryl diazonium agents that selectively crosslink monomethyllysine (Kme1) so that tryptic Kme1 peptides could be enriched for proteomic analysis. A record number of methyllysine sites were identified and a significant amount of SAM-independent lysine methylation was revealed. We hope the sulfonium and diazonium tools can be widely applied to expand our knowledge of lysine methylation.
代表性论文:
2. Yan, L.; Zheng, M.; Fan, M.; Yao, R.; Zou, K.; Feng, S.; Wu, M.*, A Chemo-selective Enrichment Strategy to Achieve In-depth Coverage of Methyllysine Proteome. Angew. Chem. Int. Ed. 2024, e202408564.