♦ See referenced article, J. Biol. Chem. 2012, 287, 36651–36661
Phosphorylase kinase (PhK), a 1.3-MDa enzyme in the activation cascade of glycogenolysis, is activated by phosphorylation by cAMP-dependent protein kinase. This activation is predominantly caused by phosphorylation of the β subunits in the (αβγδ)4 PhK complex. Despite being the first protein kinase discovered, the large size of PhK has hampered structural analyses. Electron microscopy shows it to consist of two (αβγδ)2 lobes connected by four central bridges, whose positioning changes upon activation. In this Paper of the Week, a team led by Gerald M. Carlson of the University of Kansas Medical Center used chemical, biochemical, biophysical, and computational techniques to analyze the secondary, tertiary, and quaternary structures of the PhK β subunits. They found them to be highly helical with their N and C termini proximal, forming a β4-bridged core within the complex. These results explain previous findings that the β subunits and catalytic γ subunits of PhK are structurally coupled to each other and to the enzyme's activation.
Published online: October 26, 2012
© 2012 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology.