Protein phosphatase inhibitor 2 (I-2)  -  Protein phosphatase 1

Biological function
Protein phosphatase 1 controls a multitude of cellular processes from glycogen metabolism to cell cycle, gene expression and neuronal activity. I-2 is a PP1 regulator, widely expressed from yeast to man.

Structural evidence
Three distinct segments are visible, i.e. adopt a structure in the complex: the 12-17, 44-56 and 130-169. The linkers connecting these ordered regions as well as the flanking N- and C-terminal regions are invisible in the electron density.

Biochemical evidence
I-2 binds with high affinity (Kd ~ 2nM). Deletion construct Δ77-81 - which is not ordered in the complex - suggests that this region is critical for ATP-Mg-dependent phosphatase activity. The construct lacking the C-terminal 59 residues could not be re- activated by GSK3.

Interaction specificity arises from i) hydrophobic contacts and hydrogen bonds (region I); charged and aromatic (KSQKW; region II). Residues 148-151 of I-2 interact with the catalytic center.

Mechanism category

Posttranslational modification
Phosphorylation reactivates the PP1-I-2 complex at the Thr74, which is invisible in the non-phosphorylated complex.

Isoforms, context-dependence
Isoform specificity of PP1 stems from the C terminal region, which embeds the RVxF groove. In case of I-2 the second interaction site contacts this region.

Invisible parts of the complex are responsible for intricate regulatory behavior of I-2 and contribute to converting the active to inactive conformation and vice versa.