title: Structural basis for the recognition of regulatory subunits by the catalytic subunit of protein phosphatase 1.
abstract: The diverse forms of protein phosphatase 1 in vivo result from the association of its catalytic subunit (PP1c) with different regulatory subunits, one of which is the G-subunit (G(M)) that targets PP1c to glycogen particles in muscle. Here we report the structure, at 3.0 A 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 those in the Arg/Lys-Val/Ile-Xaa-Phe motif that is present in almost every other identified mammalian PP1-binding subunit. Disrupting this motif in the G(M[63-75]) peptide and the M(110[1-38]) peptide (which mimics the myofibrillar targeting M110 subunit in stimulating the dephosphorylation of myosin) prevents these peptides from interacting with PP1. A short peptide from the PP1-binding protein p53BP2 that contains the RVXF motif also interacts with PP1c. These findings identify a recognition site on PP1c, invariant from yeast to humans, for a critical structural motif on regulatory subunits. This explains why the binding of PP1 to its regulatory subunits is mutually exclusive, and suggests a novel approach for identifying the functions of PP1-binding proteins whose roles are unknown.
authors.affiliation: Laboratory of Molecular Biophysics, University of Oxford, UK.
authors.forename: M P
authors.initials: MP
authors.lastname: Egloff
authors.forename: D F
authors.initials: DF
authors.lastname: Johnson
authors.forename: G
authors.initials: G
authors.lastname: Moorhead
authors.forename: P T
authors.initials: PT
authors.lastname: Cohen
authors.forename: P
authors.initials: P
authors.lastname: Cohen
authors.forename: D
authors.initials: D
authors.lastname: Barford
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D002384:Catalysis; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000201:enzymology; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000737:chemistry* / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D054645:Protein Phosphatase 1; D011817:Rabbits; D012441:Saccharomyces cerevisiae; D016415:Sequence Alignment; D012694:Serine / Q000737:chemistry
chemical_list: D000596:Amino Acids; D010455:Peptides; D012694:Serine; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1