Structural basis for the recognition of regulatory subunits by the catalytic subunit of protein phosphatase 1

Marie Pierre Egloff, Deborah F. Johnson, Greg Moorhead, Patricia T.W. Cohen, Philip Cohen, David Barford

    Research output: Contribution to journalArticlepeer-review

    551 Citations (Scopus)

    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 Å 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 moth that is present in almost every other identified mammalian PP1-binding subunit. Disrupting this moth in the G(M[63-75]) peptide and the M(110[1-38]) peptide (which mimics the myofibrillar targeting Mile 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 PPlc. 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.

    Original languageEnglish
    Pages (from-to)1876-1887
    Number of pages12
    JournalEMBO Journal
    Volume16
    Issue number8
    DOIs
    Publication statusPublished - 15 Apr 1997

    Keywords

    • Protein phosphatase 1
    • Recognition motif
    • Recognition site
    • Regulatory subunits
    • X-ray crystallography

    ASJC Scopus subject areas

    • General Neuroscience
    • Molecular Biology
    • General Immunology and Microbiology
    • General Biochemistry,Genetics and Molecular Biology

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