Allosteric cooperativity in protein kinase A

Larry R. Masterson, Alessandro Mascioni, Nathaniel J. 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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Keywords

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

ASJC Scopus subject areas

  • General

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