Structure of a ribonucleotide reductase R2 protein radical

DOI: 10.1126/science.adh8160

Authors: Hugo Lebrette (Stockholm University; CNRS, Université Toulouse III) , Vivek Srinivas (Stockholm University) , Juliane John (Stockholm University) , Oskar Aurelius (Stockholm University; MAX IV Laboratory, Lund University) , Rohit Kumar (Stockholm University) , Daniel Lundin (Stockholm University) , Aaron S. Brewster (Lawrence Berkeley National Laboratory) , Asmit Bhowmick (Lawrence Berkeley National Laboratory) , Abhishek Sirohiwal (Stockholm University) , In-Sik Kim (Lawrence Berkeley National Laboratory) , Sheraz Gul (Lawrence Berkeley National Laboratory) , Cindy Pham (Lawrence Berkeley National Laboratory) , Kyle D. Sutherlin (Lawrence Berkeley National Laboratory) , Philipp Simon (Lawrence Berkeley National Laboratory) , Agata Butryn (Diamond Light Source; Research Complex at Harwell) , Pierre Aller (Diamond Light Source; Research Complex at Harwell) , Allen M. Orville (Diamond Light Source; Research Complex at Harwell) , Franklin D. Fuller (LCLS, SLAC National Accelerator Laboratory) , Roberto Alonso-Mori (LCLS, SLAC National Accelerator Laboratory) , Alexander Batyuk (LCLS, SLAC National Accelerator Laboratory) , Nicholas K. Sauter (Lawrence Berkeley National Laboratory) , Vittal K. Yachandra (Lawrence Berkeley National Laboratory) , Junko Yano (Lawrence Berkeley National Laboratory,) , Ville R. I. Kaila (Stockholm University) , Britt-Marie Sjöberg (Stockholm University) , Jan Kern (Lawrence Berkeley National Laboratory) , Katarina Roos (Uppsala University) , Martin Högbom (Stockholm University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Science , VOL 382 , PAGES 109 - 113

State: Published (Approved)
Published: October 2023

Abstract: 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.

Subject Areas: Biology and Bio-materials, Chemistry, Medicine

Diamond Offline Facilities: XFEL-Hub

Facility: X06SA (PXI) at SLS; PROXIMA 1, PROXIMA 2A at SOLEIL

Added On: 12/10/2023 08:28

Discipline Tags:

Health & Wellbeing Biochemistry Chemistry Structural biology Drug Discovery Life Sciences & Biotech

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