Speaker: Chang Cui, Assistant Professor of Biochemistry, UIUC

Time: 15:00–16:30, December 25, 2025

Abstract

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.

Biography

Chang Cui is the assistant professor of biochemistry in the School of Molecular & Cellular Biology at the University of Illinois Urbana-Champaign (UIUC). She earned her B.S. in Chemistry from Peking University, Ph.D. in Chemistry from UIUC, and conducted postdoctoral research at Harvard University and MIT.

Her lab employs a combination of unnatural amino acid mutagenesis, spectroscopic and kinetic techniques, cryo-electron microscopy and cell biology methods to investigate the mechanisms of radical enzymes and long-range electron transfer.