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.