3v4y

From Proteopedia

(Difference between revisions)

Revision as of 09:47, 5 August 2016

Crystal Structure of the first Nuclear PP1 holoenzyme

Structural highlights

3v4y is a 8 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	3egg, 3egh, 3hvq
Gene:	PPP1A, PPP1CA (HUMAN), PPP1R8, ARD1, NIPP1 (HUMAN)
Activity:	Phosphoprotein phosphatase, with EC number 3.1.3.16
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[PP1A_HUMAN] Protein phosphatase that associates with over 200 regulatory proteins to form highly specific holoenzymes which dephosphorylate hundreds of biological targets. Protein phosphatase 1 (PP1) is essential for cell division, and participates in the regulation of glycogen metabolism, muscle contractility and protein synthesis. Involved in regulation of ionic conductances and long-term synaptic plasticity. May play an important role in dephosphorylating substrates such as the postsynaptic density-associated Ca(2+)/calmodulin dependent protein kinase II. Component of the PTW/PP1 phosphatase complex, which plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Regulates NEK2 function in terms of kinase activity and centrosome number and splitting, both in the presence and absence of radiation-induced DNA damage. Regulator of neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development.^[1] [PP1R8_HUMAN] Inhibitor subunit of the major nuclear protein phosphatase-1 (PP-1). It has RNA-binding activity but does not cleave RNA and may target PP-1 to RNA-associated substrates. May also be involved in pre-mRNA splicing. Binds DNA and might act as a transcriptional repressor. Seems to be required for cell proliferation. Isoform Gamma is a site-specific single-strand endoribonuclease that cleaves single strand RNA 3' to purines and pyrimidines in A+U-rich regions. It generates 5'-phosphate termini at the site of cleavage. This isoform does not inhibit PP-1. May be implicated in mRNA splicing.

Publication Abstract from PubMed

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 alpha 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 PhiPhi 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.

The molecular basis for substrate specificity of the nuclear NIPP1:PP1 holoenzyme.,O'Connell N, Nichols SR, Heroes E, Beullens M, Bollen M, Peti W, Page R Structure. 2012 Oct 10;20(10):1746-56. doi: 10.1016/j.str.2012.08.003. Epub 2012 , Aug 30. PMID:22940584^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mi J, Guo C, Brautigan DL, Larner JM. Protein phosphatase-1alpha regulates centrosome splitting through Nek2. Cancer Res. 2007 Feb 1;67(3):1082-9. PMID:17283141 doi:10.1158/0008-5472.CAN-06-3071
↑ O'Connell N, Nichols SR, Heroes E, Beullens M, Bollen M, Peti W, Page R. The molecular basis for substrate specificity of the nuclear NIPP1:PP1 holoenzyme. Structure. 2012 Oct 10;20(10):1746-56. doi: 10.1016/j.str.2012.08.003. Epub 2012 , Aug 30. PMID:22940584 doi:http://dx.doi.org/10.1016/j.str.2012.08.003

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3v4y"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of the first Nuclear PP1 holoenzyme==
 <StructureSection load='3v4y' size='340' side='right' caption='[[3v4y]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPP1A, PPP1CA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), PPP1R8, ARD1, NIPP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Phosphoprotein_phosphatase Phosphoprotein phosphatase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.1.3.16 3.1.3.16] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3v4y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v4y OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3v4y RCSB], [http://www.ebi.ac.uk/pdbsum/3v4y PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3v4y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3v4y OCA], [http://pdbe.org/3v4y PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3v4y RCSB], [http://www.ebi.ac.uk/pdbsum/3v4y PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3v4y ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3v4y" style="background-color:#fffaf0;"></div>
 ==See Also==

3v4y

From Proteopedia

Revision as of 09:47, 5 August 2016

Crystal Structure of the first Nuclear PP1 holoenzyme

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox