Structure of a ribonucleotide reductase R2 protein radical

• 成果类型: Article
• 署名作者: Lebrette, Hugo; Srinivas, Vivek; John, Juliane; Aurelius, Oskar; Kumar, Rohit; Lundin, Daniel; Brewster, Aaron S.; Bhowmick, Asmit; Sirohiwal, Abhishek; Kim, In-Sik; Gul, Sheraz; Pham, Cindy; Sutherlin, Kyle D.; Simon, Philipp; Butryn, Agata; Aller, Pierre; Orville, Allen M.; Fuller, Franklin D.; Alonso-Mori, Roberto; Batyuk, Alexander; Sauter, Nicholas K.; Yachandra, Vittal K.; Yano, Junko; Kaila, Ville R. I.; Sjoberg, Britt-Marie; Kern, Jan; Roos, Katarina; Hogbom, Martin
• 署名单位: Stockholm University; Universite de Toulouse; Universite Toulouse III - Paul Sabatier; Centre National de la Recherche Scientifique (CNRS); Lund University; United States Department of Energy (DOE); Lawrence Berkeley National Laboratory; Diamond Light Source; Stanford University; United States Department of Energy (DOE); SLAC National Accelerator Laboratory; Uppsala University; Francis Crick Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-10448
• DOI: 10.1126/science.adh8160
• 发表日期: 2023-10-06
• 页码: 109-113
• 关键词: coupled electron-transfer; high-field epr; crystal-structure; hydrogen-bonds; iron; crystallography; activation; inhibition; chemistry; cofactor

摘要

Aerobic ribonucleotide reductases (RNRs) initiate synthesis of DNA building blocks by generating a free radical within the R2 subunit; the radical is subsequently shuttled to the catalytic R1 subunit through proton-coupled electron transfer (PCET). We present a high-resolution room temperature structure of the class Ie R2 protein radical captured by x-ray free electron laser serial femtosecond crystallography. The structure reveals conformational reorganization to shield the radical and connect it to the translocation path, with structural changes propagating to the surface where the protein interacts with the catalytic R1 subunit. Restructuring of the hydrogen bond network, including a notably short O-O interaction of 2.41 angstroms, likely tunes and gates the radical during PCET. These structural results help explain radical handling and mobilization in RNR and have general implications for radical transfer in proteins.