Allosteric cooperativity in protein kinase A.
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.
Masterson
Larry R
LR
Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA.
Mascioni
Alessandro
A
Traaseth
Nathaniel J
NJ
Taylor
Susan S
SS
Veglia
Gianluigi
G
D000266:Adenylyl Imidodiphosphate; D000495:Allosteric Site; D020134:Catalytic Domain; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000737:chemistry; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry*; D007700:Kinetics; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009690:Nucleic Acid Conformation; D009711:Nucleotides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D015398:Signal Transduction
D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D008024:Ligands; D009711:Nucleotides; D000266:Adenylyl Imidodiphosphate; D017868:Cyclic AMP-Dependent Protein Kinases