PP1 regulatory protein binding pockets are differentially conserved in PPZ1. (A) Sequence conservation between PPZ1 and PP1α mapped onto the surface of PPZ1. The yellow star indicates the location of the PP1 active site. (B) Close-up views of the RVxF, ΦΦ, SILK, I-2 helix, MyPhoNE helix, and NIPP1 helix binding pockets on PPZ1, with regulators that bind these pockets shown as sticks (RVxF, ΦΦ, and SILK) or a cartoon (I-2 helix, MyPhoNE helix, and NIPP1 helix). The sequence changes between PP1α/PPZ1 are indicated as in panel A. The sequence identity of the binding pockets is reported (see Fig. S1 in the supplemental material). (C) Overlay of a PP1 regulator (PNUTS [shown here in orange]) that bridges the ΦΦ and Arg motif binding pockets onto PPZ1cat (rose). The clash between the regulator and Z1-specific helix is shown.