Structural analysis of the protein phosphatase 1 docking motif: molecular description of binding specificities identifies interacting proteins.
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.
Meiselbach
Heike
H
Emil-Fischer-Zentrum, Institut für Biochemie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany.
Sticht
Heinrich
H
Enz
Ralf
R
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D024322:Amino Acids, Aromatic / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D016384:Consensus Sequence; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010749:Phosphoprotein Phosphatases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054645:Protein Phosphatase 1; D017434:Protein Structure, Tertiary; D051381:Rats; D012680:Sensitivity and Specificity; D013379:Substrate Specificity; D014633:Valine / Q000235:genetics / Q000378:metabolism
D024322:Amino Acids, Aromatic; D008024:Ligands; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D014633:Valine