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Mol Cell. 2016 Aug 18;63(4):686-695. doi: 10.1016/j.molcel.2016.06.024. Epub 2016 Jul 21.

A Conserved Motif Provides Binding Specificity to the PP2A-B56 Phosphatase.

Author information

1
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
2
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. Electronic address: thomas.kruse@cpr.ku.dk.
3
Conway Institute of Biomolecular and Biomedical Sciences, University College Dublin, Dublin 4, Ireland.
4
Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark. Electronic address: jakob.nilsson@cpr.ku.dk.

Abstract

Dynamic protein phosphorylation is a fundamental mechanism regulating biological processes in all organisms. Protein phosphatase 2A (PP2A) is the main source of phosphatase activity in the cell, but the molecular details of substrate recognition are unknown. Here, we report that a conserved surface-exposed pocket on PP2A regulatory B56 subunits binds to a consensus sequence on interacting proteins, which we term the LxxIxE motif. The composition of the motif modulates the affinity for B56, which in turn determines the phosphorylation status of associated substrates. Phosphorylation of amino acid residues within the motif increases B56 binding, allowing integration of kinase and phosphatase activity. We identify conserved LxxIxE motifs in essential proteins throughout the eukaryotic domain of life and in human viruses, suggesting that the motifs are required for basic cellular function. Our study provides a molecular description of PP2A binding specificity with broad implications for understanding signaling in eukaryotes.

PMID:
27453045
DOI:
10.1016/j.molcel.2016.06.024
[Indexed for MEDLINE]
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