%0 Journal Article
%T Novel ATP-cone-driven allosteric regulation of ribonucleotide reductase via the radical-generating subunit.
%A Rozman Grinberg I
%A Lundin D
%A Hasan M
%A Crona M
%A Jonna VR
%A Loderer C
%A Sahlin M
%A Markova N
%A Borovok I
%A Berggren G
%A Hofer A
%A Logan DT
%A Sjöberg BM
%J Elife
%V 7
%N 0
%D 02 2018 1
%M 29388911
%F 8.713
%R 10.7554/eLife.31529
%X 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.