Allosteric cooperativity in protein kinase A

Larry R. Masterson, Alessandro Mascioni, Nathaniel Traaseth, Susan S. Taylor, Gianluigi Veglia

Research output: Contribution to journalArticle

Abstract

Allosteric signaling in proteins requires long-range communication mediated by highly conserved residues, often triggered by ligand binding. In this article, we map the allosteric network in the catalytic subunit of protein kinase A using NMR spectroscopy. We show that positive allosteric cooperativity is generated by nucleotide and substrate binding during the transitions through the major conformational states: apo, intermediate, and closed. The allosteric network is disrupted by a single site mutation (Y204A), which also decouples the cooperativity of ligand binding. Because protein kinase A is the prototype for the entire kinome, these findings may serve as a paradigm for describing long-range coupling in other protein kinases.

Original languageEnglish (US)
Pages (from-to)506-511
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number2
DOIs
StatePublished - Jan 15 2008

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Cyclic AMP-Dependent Protein Kinases
Cyclic AMP-Dependent Protein Kinase Catalytic Subunits
Ligands
Protein Kinases
Magnetic Resonance Spectroscopy
Nucleotides
Mutation
Proteins

Keywords

  • Allostery
  • Chemical shift mapping
  • Enzymes
  • NMR
  • Signaling

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Allosteric cooperativity in protein kinase A. / Masterson, Larry R.; Mascioni, Alessandro; Traaseth, Nathaniel; Taylor, Susan S.; Veglia, Gianluigi.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 105, No. 2, 15.01.2008, p. 506-511.

Research output: Contribution to journalArticle

Masterson, Larry R. ; Mascioni, Alessandro ; Traaseth, Nathaniel ; Taylor, Susan S. ; Veglia, Gianluigi. / Allosteric cooperativity in protein kinase A. In: Proceedings of the National Academy of Sciences of the United States of America. 2008 ; Vol. 105, No. 2. pp. 506-511.
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