Enzymatically Active Mammalian Ribonucleotide Reductase Exists Primarily as an α6β2 Octamer*

By R. Rofougaran, M. Vodnala, A. Hofer. Journal of Biological Chemistry, 2006

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Ribonucleotide reductase synthesizes deoxyribonucleotides, which are essential building blocks for DNA synthesis. The mammalian ribonucleotide reductase is described as an α2β2 complex consisting of R1 (α) and R2 (β) proteins. ATP stimulates and dATP inhibits enzyme activity by binding to an allosteric site called the activity site on the R1 protein. Despite the opposite effects by ATP and dATP on enzyme activity, both nucleotides induce formation of R1 oligomers. By using a new technique termed Gas-phase Electrophoretic-Mobility Macromolecule Analysis (GEMMA), we have found that the ATP/dATP-induced R1 oligomers have a defined size (hexamers) and can interact with the R2 dimer to form an enzymatically active protein complex (α6β2). The newly discovered α6β2 complex can either be in an active or an inhibited state depending on whether ATP or dATP is bound. Our results suggest that this protein complex is the major form of ribonucleotide reductase at physiological levels of R1-R2 protein and nucleotides.

Subfields: Inorganic Chemistry, Materials Chemistry, Spectroscopy

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