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

Summary, in English

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.

• Författare: Renzo Johansson; Venkateswara Rao Jonna; Rohit Kumar; Niloofar Nayeri; Daniel Lundin; Britt Marie Sjöberg; Anders Hofer; Derek T. Logan
• Avdelning/ar: Biokemi och Strukturbiologi
• Publiceringsår: 2016-06-07
• Språk: Engelska
• Sidor: 906-917
• Publikation/Tidskrift/Serie: Structure
• Volym: 24
• Issue: 6
• Länkar: http://dx.doi.org/10.1016/j.str.2016.03.025
• Dokumenttyp: Artikel i tidskrift
• Förlag: Cell Press
• Ämne: Structural Biology
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 0969-2126