3V4Y

Crystal Structure of the first Nuclear PP1 holoenzyme

Summary for 3V4Y

• Entry DOI: 10.2210/pdb3v4y/pdb
• Related: 3EGG 3EGH 3HVQ
• Descriptor: Serine/threonine-protein phosphatase PP1-alpha catalytic subunit, Nuclear inhibitor of protein phosphatase 1, MANGANESE (II) ION, ... (6 entities in total)
• Functional Keywords: pp1, ser/thr phosphatase, nipp1, idp, hydrolase
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P62136; Nucleus. Isoform Gamma: Cytoplasm: Q12972
• Total number of polymer chains: 8
• Total formula weight: 171509.85

Authors

Page, R.,Peti, W.,O'Connell, N.E.,Nichols, S. (deposition date: 2011-12-15, release date: 2012-10-31, Last modification date: 2024-02-28)

Primary citation

O'Connell, N.,Nichols, S.R.,Heroes, E.,Beullens, M.,Bollen, M.,Peti, W.,Page, R.
The Molecular Basis for Substrate Specificity of the Nuclear NIPP1:PP1 Holoenzyme.
Structure, 20:1746-1756, 2012

PubMed 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.

PubMed: 22940584
DOI: 10.1016/j.str.2012.08.003

Experimental method

X-RAY DIFFRACTION (2.098 Å)