title: Enzymatically active mammalian ribonucleotide reductase exists primarily as an alpha6beta2 octamer.
abstract: Ribonucleotide reductase synthesizes deoxyribonucleotides, which are essential building blocks for DNA synthesis. The mammalian ribonucleotide reductase is described as an alpha(2)beta(2) complex consisting of R1 (alpha) and R2 (beta) 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 (alpha(6)beta(2)). The newly discovered alpha(6)beta(2) 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.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Umeå University, SE-901 87 Umeå, Sweden.
authors.forename: Reza
authors.initials: R
authors.lastname: Rofougaran
authors.forename: Munender
authors.initials: M
authors.lastname: Vodnala
authors.forename: Anders
authors.initials: A
authors.lastname: Hofer
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002850:Chromatography, Gel; D019281:Dimerization; D004586:Electrophoresis; D013058:Mass Spectrometry; D051379:Mice; D020836:Protein Structure, Quaternary; D012264:Ribonucleotide Reductases / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000255:Adenosine Triphosphate; D012264:Ribonucleotide Reductases