各位老师和同学：
大家好，2025年12月26日（星期五），化学生物学与生物技术学院邀请了University of Illinois Urbana-Champaign化学生物学系的崔畅助理教授到访我院并进行化学生物学前沿讲座，欢迎大家参加！
嘉 宾：崔畅 助理教授
嘉宾单位：Department of Biochemistry, University of Illinois Urbana-Champaign
主 题：Radical Trap Reveals Activation Pathway of Human Ribonucleotide Reductase
时 间：2025年12月26日（星期五）15：00-16：30
地 点：C103
邀请人：姜延龙
讲座摘要：
The active form of human ribonucleotide reductase (RNR), essential for DNA synthesis, has remained elusive due to the dynamic, transient nature of the α/β interactions. Although α6β2 and α6β6 assemblies have long been proposed as functional forms, structural studies of dATP-inhibited α6 reveal a compact ring that blocks β2 binding. How this autoinhibited α6 reorganizes into an active complex has remained a long-standing puzzle that cannot be solved by structural or enzymological studies alone, but requires structural snapshots informed by a mechanistic understanding of radical transfer. Here, we genetically encoded DOPA as a radical trap to capture human RNR in a pre-turnover state, enabling high-resolution cryoEM analysis. We visualized the canonical α2β2 complex alongside an intermediate α3β2 and a series of α oligomers, revealing a trajectory in which α architectures govern β2 docking. The compact α6 ring likely enforces autoinhibition by blocking β2, whereas expansion to α8 ring or partial disassembly to α5 allows docking and catalysis. This integrated approach illuminates the structural basis of human RNR activation and provides a framework for developing next-generation inhibitors targeting radical transfer or allosteric regulation.
嘉宾简介：
崔畅，女，伊利诺伊大学香槟分校生物化学系助理教授、博士生导师。2012年本科毕业于北京大学化学与分子工程学院，2018年博士毕业于伊利诺伊大学香槟分校化学系，同年到哈佛大学和麻省理工大学从事博士后研究。2023年底加入伊利诺伊大学香槟分校，主要研究方向为金属及自由基酶学及生物无机化学。至今在JACS, PNAS, Angew Chem等国际著名刊物上发表SCI论文20余篇。曾获Carver Charitable Trust New Investigator Award 2025。
