Abstract

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.

Details

Title
Convergent allostery in ribonucleotide reductase
Author
Thomas, William C 1 ; Brooks, F Phil, III 2 ; Burnim, Audrey A 1   VIAFID ORCID Logo  ; John-Paul Bacik 1 ; Stubbe, JoAnne 3 ; Kaelber, Jason T 4   VIAFID ORCID Logo  ; Chen, James Z 5 ; Ando, Nozomi 1 

1  Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, USA; Department of Chemistry, Princeton University, Princeton, NJ, USA 
2  Department of Chemistry, Princeton University, Princeton, NJ, USA 
3  Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, USA 
4  Institute for Quantitative Biomedicine, Rutgers University, Piscataway, NJ, USA 
5  Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Portland, OR, USA 
Pages
1-13
Publication year
2019
Publication date
Jun 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-10568-4
ProQuest document ID
2240137707
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.