STRUCTURAL BASIS FOR THE RECOGNITION OF REGULATORY SUBUNITS BY THE CATALYTIC SUBUNIT OF PROTEIN-PHOSPHATASE-1

The diverse forms of protein phosphatase 1 in vivo result from the ass ociation of its catalytic subunit (PP1c) with different regulatory sub units, one of which is the G-subunit (G(M)) that targets PP1c to glyco gen particles in muscle, Here we report the structure, at 3.0 Angstrom resolution, of PP1c in complex with a 13 residue peptide (G(M[63-75]) ) of G(M). The residues in G(M[63-75]) that interact with PP1c are tho se in the Arg/Lys-Val/Ile-Xaa-Phe motif that is present in almost ever y other identified mammalian PP1-binding subunit. Disrupting this moti f in the G(M[63-75]) peptide and the M110[1-38] peptide (which mimics the myofibrillar targeting M-110 subunit in stimulating the dephosphor ylation of myosin) prevents these peptides from interacting with PP1. A short peptide from the PP1-binding protein p53BP2 that contains the RVXF moth also interacts with PP1c. These findings identify a recognit ion site on PP1c, invariant from yeast to humans, for a critical struc tural motif on regulatory subunits. This explains why the binding of P P1 to its regulatory subunits is mutually exclusive, and suggests a no vel approach for identifying the functions of PP1-binding proteins who se roles are unknown.