29.08.2024 - 08:43:16

Alternating binding and p97-mediated dissociation of SDS22 and I3 recycles active PP1 between holophosphatases

The Meyer Lab has published a new paper in PNAS. Dephosphorylation of diverse cellular targets is catalyzed by Protein phosphatase-1. Its catalytic subunit (PP1) therefore joins diverse targeting subunits to form holophosphatases. During holophosphatase biogenesis newly synthesized PP1 is trapped in an inhibitory complex with Suppressor-of-Dis2-number-2 (SDS22) and Inhibitor-3 (I3). This inhibitory SDS22-PP1-I3 complex is then disassembled by the ATPases Associated with diverse cellular Activities plus (AAA+) protein p97. Using Förster Resonance energy transfer (FRET) analysis of labeled proteins they show, that this mechanism extends to mature PP1 and that cycles of SDS22-PP1-I3 formation and p97-driven disassembly regulate dynamic exchange of PP1 to match holophosphatase composition to changing physiological conditions.