Structural analysis of the protein phosphatase 1 docking motif: molecular description of binding specificities identifies interacting proteins

Chem Biol. 2006 Jan;13(1):49-59. doi: 10.1016/j.chembiol.2005.10.009.


The interplay between kinases and phosphatases represents a fundamental regulatory mechanism in biological systems. Being less numerous than kinases, phosphatases increase their diversity by the acquisition of a variety of binding partners, thereby forming a large number of holoenzymes. Proteins interacting with protein phosphatase 1 (PP1) often bind via a so-called docking motif to regulate its enzymatic activity, substrate specificity, and subcellular localization. Here, we systematically determined structural elements that mediate the binding specificity of PP1 interacting proteins, and propose a refined consensus sequence for high-affinity PP1 ligands. Applying this pattern to database searches, we predicted and experimentally confirmed several previously unknown PP1 interactors. Thus, the suggested PP1 docking motif enables a highly specific prediction of PP1 binding partners, thereby facilitating the genome-wide identification of PP1 interactors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Amino Acids, Aromatic / chemistry
  • Amino Acids, Aromatic / metabolism
  • Animals
  • Binding Sites
  • Consensus Sequence
  • Ligands
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation / genetics
  • Phosphoprotein Phosphatases / chemistry*
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / metabolism*
  • Protein Binding
  • Protein Phosphatase 1
  • Protein Structure, Tertiary
  • Rats
  • Sensitivity and Specificity
  • Substrate Specificity
  • Valine / genetics
  • Valine / metabolism


  • Amino Acids, Aromatic
  • Ligands
  • Phosphoprotein Phosphatases
  • Protein Phosphatase 1
  • Valine