eLife (Feb 2018)

Novel ATP-cone-driven allosteric regulation of ribonucleotide reductase via the radical-generating subunit

  • Inna Rozman Grinberg,
  • Daniel Lundin,
  • Mahmudul Hasan,
  • Mikael Crona,
  • Venkateswara Rao Jonna,
  • Christoph Loderer,
  • Margareta Sahlin,
  • Natalia Markova,
  • Ilya Borovok,
  • Gustav Berggren,
  • Anders Hofer,
  • Derek T Logan,
  • Britt-Marie Sjöberg

DOI
https://doi.org/10.7554/eLife.31529
Journal volume & issue
Vol. 7

Abstract

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Ribonucleotide reductases (RNRs) are key enzymes in DNA metabolism, with allosteric mechanisms controlling substrate specificity and overall activity. In RNRs, the activity master-switch, the ATP-cone, has been found exclusively in the catalytic subunit. In two class I RNR subclasses whose catalytic subunit lacks the ATP-cone, we discovered ATP-cones in the radical-generating subunit. The ATP-cone in the Leeuwenhoekiella blandensis radical-generating subunit regulates activity via quaternary structure induced by binding of nucleotides. ATP induces enzymatically competent dimers, whereas dATP induces non-productive tetramers, resulting in different holoenzymes. The tetramer forms by interactions between ATP-cones, shown by a 2.45 Å crystal structure. We also present evidence for an MnIIIMnIV metal center. In summary, lack of an ATP-cone domain in the catalytic subunit was compensated by transfer of the domain to the radical-generating subunit. To our knowledge, this represents the first observation of transfer of an allosteric domain between components of the same enzyme complex.

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