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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • 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
Organisations
External organisations
  • Stockholm University
  • Umeå University
  • Tel-Aviv University
  • Uppsala University
  • Swedish Orphan Biovitrum
  • Malvern Instruments Inc.
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biochemistry and Molecular Biology
Original languageEnglish
Article numbere31529
JournaleLife
Volume7
Publication statusPublished - 2018 Feb 1
Publication categoryResearch
Peer-reviewedYes