Advanced

Structural Mechanism of Allosteric Activity Regulation in a Ribonucleotide Reductase with Double ATP Cones

Johansson, Renzo LU ; Jonna, Venkateswara Rao; Kumar, Rohit LU ; Nayeri, Niloofar; Lundin, Daniel; Sjöberg, Britt Marie; Hofer, Anders and Logan, Derek T. LU (2016) In Structure 24(6). p.906-917
Abstract

Summary 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... (More)

Summary 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.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Structure
volume
24
issue
6
pages
12 pages
publisher
Cell Press
external identifiers
  • scopus:84964594794
  • wos:000377782200011
ISSN
0969-2126
DOI
10.1016/j.str.2016.03.025
language
English
LU publication?
yes
id
8888abe5-8991-468e-9dcd-a9ebcff6b05a
date added to LUP
2016-10-04 15:06:17
date last changed
2017-01-01 08:35:58
@article{8888abe5-8991-468e-9dcd-a9ebcff6b05a,
  abstract     = {<p>Summary 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.</p>},
  author       = {Johansson, Renzo and Jonna, Venkateswara Rao and Kumar, Rohit and Nayeri, Niloofar and Lundin, Daniel and Sjöberg, Britt Marie and Hofer, Anders and Logan, Derek T.},
  issn         = {0969-2126},
  language     = {eng},
  month        = {06},
  number       = {6},
  pages        = {906--917},
  publisher    = {Cell Press},
  series       = {Structure},
  title        = {Structural Mechanism of Allosteric Activity Regulation in a Ribonucleotide Reductase with Double ATP Cones},
  url          = {http://dx.doi.org/10.1016/j.str.2016.03.025},
  volume       = {24},
  year         = {2016},
}