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. Author manuscript; available in PMC: 2017 Mar 1.
Published in final edited form as: FEBS J. 2015 Nov 14;283(6):1004–1024. doi: 10.1111/febs.13573

Figure 2.

Figure 2

Structures of PP2A core enzyme and holoenzyme. (A) (PDB code: 2IE3) Core Enzyme consisting of Aα (in magenta) subunit and Cα (in yellow) subunit. The C subunit binds A at Heat Repeats 11–15. The active site of the C subunit consists of 2 manganese atoms and is positioned away from the ridge of the A subunit HEAT Repeats. Binding with the catalytic subunit shifts HEAT repeats 13–15 by 20–30 Å (B) (PDB code: 3DW8) Core Enzyme binding to B family subunit (in cyan), Bα/PR55α. Members of this subunit family bind the A subunit at two interfaces. The first is via a seven bladed propeller, composed of WD40 repeats. The bottom face of the propeller binds to A subunit HEAT domains 3–7. The second is through a β-hairpin handle that interacts with A subunit HEAT repeats 1 and 2. Upon binding to the holoenzyme, the B subunit substrate binding site lies on the top face proximal to the active site of the catalytic subunit. (C) (PDB code: 2IAE) Core enzyme binding to B′ family subunit (in cyan), Bγ1/PR61γ1. The B′ structures are similar to the A subunit, composed of 8 HEAT-like repeats. These interact with HEAT repeats 2–8 of the A subunit, and with the C subunit. Much like binding to B family subunits, the substrate binding site of B′ is proximal to the active site of the catalytic subunit upon holoenzyme formation. Binding to the B′ subunits forces the N-terminal repeat of the A subunit to twist 50–60 Å, rearranging the hydrophobic core of the scaffolding subunit. (D) (PDB code: 4I5L) Core Enzyme binding to B″ family subunit PR72 (in cyan). B″ subunits consist of a linear arrangement of different functional motifs that include an N-terminal hydrophobic motif and 2 EF hand calcium binding motifs. The N-terminal hydrophobic motif and one EF hand bind to the A subunit at HEAT repeats 1–7 and binds to the catalytic subunit via a helix on the subunit at residues 439–446 near the active site, positioning the substrate binding site near the active site. The resulting conformation of this holoenzyme is wider and taller than that which forms with B or B′ subunits.