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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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.

Original languageEnglish
Article numbere31529
JournaleLife
Volume7
DOIs
StatePublished - 1 Feb 2018

Funding

FundersFunder number
Horizon 2020 Framework Programme
Wenner-Gren Stiftelserna
European Research Council
Vetenskapsrådet2016-01920, 2016-04855, 04855, 01920
CancerfondenCAN 2016/670, 721 2016/670
Svenska Forskningsrådet Formas213-2014-880
Carl Tryggers Stiftelse för Vetenskaplig Forskning621–2014-5670
H2020 European Research Council714102

    Fingerprint

    Dive into the research topics of 'Novel ATP-cone-driven allosteric regulation of ribonucleotide reductase via the radical-generating subunit'. Together they form a unique fingerprint.

    Cite this