title: Structural Mechanism of Allosteric Activity Regulation in a Ribonucleotide Reductase with Double ATP Cones.
abstract: Ribonucleotide reductases (RNRs) reduce ribonucleotides to deoxyribonucleotides. Their overall activity is stimulated by ATP and downregulated by dATP via a genetically mobile ATP cone domain mediating the formation of oligomeric complexes with varying quaternary structures. The crystal structure and solution X-ray scattering data of a novel dATP-induced homotetramer of the Pseudomonas aeruginosa class I RNR reveal the structural bases for its unique properties, namely one ATP cone that binds two dATP molecules and a second one that is non-functional, binding no nucleotides. Mutations in the observed tetramer interface ablate oligomerization and dATP-induced inhibition but not the ability to bind dATP. Sequence analysis shows that the novel type of ATP cone may be widespread in RNRs. The present study supports a scenario in which diverse mechanisms for allosteric activity regulation are gained and lost through acquisition and evolutionary erosion of different types of ATP cone.
authors.affiliation: Department of Biochemistry & Structural Biology, Lund University, Box 124, 221 00 Lund, Sweden.
authors.forename: Renzo
authors.initials: R
authors.lastname: Johansson
authors.affiliation: Department of Medical Biochemistry & Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Venkateswara Rao
authors.initials: VR
authors.lastname: Jonna
authors.affiliation: Department of Biochemistry & Structural Biology, Lund University, Box 124, 221 00 Lund, Sweden.
authors.forename: Rohit
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Department of Biochemistry & Structural Biology, Lund University, Box 124, 221 00 Lund, Sweden.
authors.forename: Niloofar
authors.initials: N
authors.lastname: Nayeri
authors.affiliation: Department of Biochemistry & Biophysics, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lundin
authors.affiliation: Department of Biochemistry & Biophysics, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Sjöberg
authors.affiliation: Department of Medical Biochemistry & Biophysics, Umeå University, 901 87 Umeå, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Hofer
authors.affiliation: Department of Biochemistry & Structural Biology, Lund University, Box 124, 221 00 Lund, Sweden. Electronic address: derek.logan@biochemistry.lu.se.
authors.forename: Derek T
authors.initials: DT
authors.lastname: Logan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000494:Allosteric Regulation; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D009154:Mutation; D011485:Protein Binding; D011487:Protein Conformation; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics; D012264:Ribonucleotide Reductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D000255:Adenosine Triphosphate; D012264:Ribonucleotide Reductases