Convergent Allostery in Ribonucleotide Reductase
| Autor: | Audrey A. Burnim, F.P. Brooks rd, James Z. Chen, JoAnne Stubbe, Nozomi Ando, William C. Thomas, Jason T. Kaelber, John-Paul Bacik |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Models Molecular Ribonucleotide ved/biology.organism_classification_rank.species General Physics and Astronomy 02 engineering and technology Bacillus subtilis Crystallography X-Ray Biochemistry 01 natural sciences Deoxyribonucleotides lcsh:Science chemistry.chemical_classification 0303 health sciences Multidisciplinary biology Chemistry SAXS 021001 nanoscience & nanotechnology Ribonucleotide reductase 0210 nano-technology Allosteric Site Stereochemistry Science Allosteric regulation 010402 general chemistry General Biochemistry Genetics and Molecular Biology Article Evolution Molecular 03 medical and health sciences Allosteric Regulation Bacterial Proteins Tetramer Oxidoreductase Ribonucleotide Reductases Scattering Small Angle Protein Structure Quaternary Model organism X-ray crystallography 030304 developmental biology DNA synthesis ved/biology Cryoelectron Microscopy Proteins General Chemistry Ribonucleotides biology.organism_classification 0104 chemical sciences 030104 developmental biology lcsh:Q Activity regulation |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-13 (2019) Nature Communications |
| DOI: | 10.1101/504290 |
| Popis: | Ribonucleotide reductases (RNRs) use a conserved radical-based mechanism to catalyze the conversion of ribonucleotides to deoxyribonucleotides. Within the RNR family, class Ib RNRs are notable for being largely restricted to bacteria, including many pathogens, and for lacking an evolutionarily mobile ATP-cone domain that allosterically controls overall activity. In this study, we report the emergence of a distinct and unexpected mechanism of activity regulation in the sole RNR of the model organism Bacillus subtilis. Using a hypothesis-driven structural approach that combines the strengths of small-angle X-ray scattering (SAXS), crystallography, and cryo-electron microscopy (cryo-EM), we describe the reversible interconversion of six unique structures, including a flexible active tetramer and two inhibited helical filaments. These structures reveal the conformational gymnastics necessary for RNR activity and the molecular basis for its control via an evolutionarily convergent form of allostery. Ribonucleotide reductase (RNR) catalyzes the conversion of ribonucleotides to deoxyribonucleotides, which is an essential step in DNA synthesis. Here the authors use small-angle X-ray scattering, X-ray crystallography, and cryo-electron microscopy to capture active and inactive forms of the Bacillus subtilis RNR and provide mechanistic insights into a convergent form of allosteric regulation. |
| Databáze: | OpenAIRE |
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