A portion of the B^'-and B-regulatory subunits contacts the active site of the C-catalytic subunit. Ribbon diagrams showing a “top-down” view of two heterotrimeric holoenzyme PP2A complexes. The subunits of the holoenzyme complexes are color-coded with the catalytic C subunit in gray, the scaffold A subunit in yellow, and B subunits in blue. The PP2A inhibitor microcystin-LR is shown near the active site as a red stick figure. (a), Structure of the PP2A/B^'γ holoenzyme (PDB 2NPP); inset highlights the infiltration of the B^'γ-subunit residue, E122 (green), into the catalytic core above. Below, sequence alignment of the B^' family of regulatory subunits with the conserved glutamate residue (green). (b), Structure of the PP2A/Bα holoenzyme (PDB 3DW8); inset shows infiltration of the Bα-subunit residues, K88 (green), into the catalytic core above. Below, sequence alignment of the B family of regulatory subunits with the conserved lysine residue (green).

Diversity of the B-regulatory subunits and the structure of the PP2A holoenzyme complex. (a) Cladogram of the human PP2A B-regulatory subunits generated using ClustalW [16] and shown with Dendroscope [17]. (b) Structure of the dimeric A scaffold subunit and C catalytic subunit (gray). The shaded portions of the A scaffold subunit indicate the known docking sites for the B regulatory subunits; green (HEAT repeat 1) for the B family of regulatory subunits, red (HEAT repeat 8) for the B^' family of regulatory subunits, and yellow (HEAT repeat 2–7) for the docking site area common for the B and B^' families. Cartoon structure of the B (green ribbon), B^' (red ribbon), B^” (purple rectangle), and B^”' (tan circle) families of regulatory subunits. Cartoon structures were generated using the Protein Data Bank accession codes 3DW8 and 2NPP.