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Title: The Molecular Basis for Substrate Specificity of the Nuclear NIPP1:PP1 Holoenzyme
Authors: O'Connell, Nichole ×
Nichols, Scott R
Heroes, Ewald
Beullens, Monique
Bollen, Mathieu
Peti, Wolfgang
Page, Rebecca #
Issue Date: Oct-2012
Publisher: Current Biology
Series Title: Structure vol:20 issue:10 pages:1746-1756
Abstract: Regulation of protein phosphatase 1 (PP1) is controlled by a diverse array of regulatory proteins. However, how these proteins direct PP1 specificity is not well understood. More than one-third of the nuclear pool of PP1 forms a holoenzyme with the nuclear inhibitor of PP1, NIPP1, to regulate chromatin remodeling, among other essential biological functions. Here, we show that the PP1-binding domain of NIPP1 is an intrinsically disordered protein, which binds PP1 in an unexpected manner. NIPP1 forms an α helix that engages PP1 at a unique interaction site, using polar rather than hydrophobic contacts. Importantly, the structure also reveals a shared PP1 interaction site outside of the RVxF motif, the ΦΦ motif. Finally, we show that NIPP1:PP1 substrate selectivity is determined by altered electrostatics and enhanced substrate localization. Together, our results provide the molecular basis by which NIPP1 directs PP1 substrate specificity in the nucleus.
URI: 
ISSN: 0969-2126
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Biosignaling & Therapeutics
× corresponding author
# (joint) last author

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