Structural interconversions modulate activity of Escherichia coli ribonucleotide reductase
Name
Ando-2011-Structural interconv.pdf
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1.43 MB
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Author(s)
Ando, Nozomi
Brignole, Edward J.
Zimanyi, Christina M.
Funk, Michael Andrew
Yokoyama, Kenichi
Asturias, Francisco J.
Stubbe, JoAnne
Drennan, Catherine L
Date Issued
December 2011
Journal
Proceedings of the National Academy of Sciences of the United States of America
Publisher
National Academy of Sciences of the United States of America
Citation
Ando, N. et al. “Structural Interconversions Modulate Activity of Escherichia Coli Ribonucleotide Reductase.” Proceedings of the National Academy of Sciences 108.52 (2011): 21046–21051. Copyright ©2011 by the National Academy of Sciences
Version
Final published version
Abstract
Essential for DNA biosynthesis and repair, ribonucleotide reductases (RNRs) convert ribonucleotides to deoxyribonucleotides via radical-based chemistry. Although long known that allosteric regulation of RNR activity is vital for cell health, the molecular basis of this regulation has been enigmatic, largely due to a lack of structural information about how the catalytic subunit (α2) and the radical-generation subunit (β2) interact. Here we present the first structure of a complex between α2 and β2 subunits for the prototypic RNR from Escherichia coli. Using four techniques (small-angle X-ray scattering, X-ray crystallography, electron microscopy, and analytical ultracentrifugation), we describe an unprecedented α4β4 ring-like structure in the presence of the negative activity effector dATP and provide structural support for an active α2β2 configuration. We demonstrate that, under physiological conditions, E. coli RNR exists as a mixture of transient α2β2 and α4β4 species whose distributions are modulated by allosteric effectors. We further show that this interconversion between α2β2 and α4β4 entails dramatic subunit rearrangements, providing a stunning molecular explanation for the allosteric regulation of RNR activity in E. coli.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Chemistry
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DOI of Published Version
https://doi.org/10.1073/pnas.1112715108
