A PROTEIN-PHOSPHORYLATION SWITCH AT THE CONSERVED ALLOSTERIC SITE IN GP

A phosphorylation-initiated mechanism of local protein refolding activ ates yeast glycogen phosphorylase (GP). Refolding of the phosphorylate d amino-terminus was shown to create a hydrophobic cluster that wedges into the subunit interface of the enzyme to trigger activation, The p hosphorylated threonine is buried in the allosteric site, The mechanis m implicates glucose 6-phosphate, the allosteric inhibitor, in facilit ating dephosphorylation by dislodging the buried covalent phosphate th rough binding competition, Thus, protein phosphorylation-dephosphoryla tion may also be controlled through regulation of the accessibility of the phosphorylation site to kinases and phosphatases. In mammalian gl ycogen phosphorylase, phosphorylation occurs at a distinct locus. The corresponding allosteric site binds a ligand activator, adenosine mono phosphate, which triggers activation by a mechanism analogous to that of phosphorylation in the yeast enzyme.