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4mp0

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Revision as of 23:53, 4 August 2016

Structure of a second nuclear PP1 Holoenzyme, crystal form 2

Structural highlights

4mp0 is a 4 chain structure with sequence from Buffalo rat and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
Related:	3v4y, 4moy
Gene:	PPP1CA, PPP1A (HUMAN), Ppp1r10, Cat53, Pnuts (Buffalo rat)
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] [PP1RA_RAT] Scaffold protein which mediates the formation of the PTW/PP1 phosphatase complex by providing a binding platform to each component of the complex. The PTW/PP1 phosphatase complex plays a role in the control of chromatin structure and cell cycle progression during the transition from mitosis into interphase. Mediates interaction of WDR82 and PPP1CA. Inhibitor of PPP1CA and PPP1CC phosphatase activities. Has inhibitory activity on PPP1CA only when phosphorylated. Binds to mRNA, single-stranded DNA (ssDNA), poly(A) and poly(G) homopolymers.^[2] ^[3]

Publication Abstract from PubMed

The serine/threonine protein phosphatase 1 (PP1) dephosphorylates hundreds of key biological targets by associating with nearly 200 regulatory proteins to form highly specific holoenzymes. However, how these proteins direct PP1 specificity and the ability to predict how these PP1 interacting proteins bind PP1 from sequence alone is still missing. PP1 nuclear targeting subunit (PNUTS) is a PP1 targeting protein that, with PP1, plays a central role in the nucleus, where it regulates chromatin decondensation, RNA processing, and the phosphorylation state of fundamental cell cycle proteins, including the retinoblastoma protein (Rb), p53, and MDM2. The molecular function of PNUTS in these processes is completely unknown. Here, we show that PNUTS, which is intrinsically disordered in its free form, interacts strongly with PP1 in a highly extended manner. Unexpectedly, PNUTS blocks one of PP1's substrate binding grooves while leaving the active site accessible. This interaction site, which we have named the arginine site, allowed us to define unique PP1 binding motifs, which advances our ability to predict how more than a quarter of the known PP1 regulators bind PP1. Additionally, the structure shows how PNUTS inhibits the PP1-mediated dephosphorylation of critical substrates, especially Rb, by blocking their binding sites on PP1, insights that are providing strategies for selectively enhancing Rb activity.

Understanding the antagonism of retinoblastoma protein dephosphorylation by PNUTS provides insights into the PP1 regulatory code.,Choy MS, Hieke M, Kumar GS, Lewis GR, Gonzalez-Dewhitt KR, Kessler RP, Stein BJ, Hessenberger M, Nairn AC, Peti W, Page R Proc Natl Acad Sci U S A. 2014 Mar 3. PMID:24591642^[4]

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
↑ Allen PB, Kwon YG, Nairn AC, Greengard P. Isolation and characterization of PNUTS, a putative protein phosphatase 1 nuclear targeting subunit. J Biol Chem. 1998 Feb 13;273(7):4089-95. PMID:9461602
↑ Kim YM, Watanabe T, Allen PB, Kim YM, Lee SJ, Greengard P, Nairn AC, Kwon YG. PNUTS, a protein phosphatase 1 (PP1) nuclear targeting subunit. Characterization of its PP1- and RNA-binding domains and regulation by phosphorylation. J Biol Chem. 2003 Apr 18;278(16):13819-28. Epub 2003 Feb 6. PMID:12574161 doi:http://dx.doi.org/10.1074/jbc.M209621200
↑ Choy MS, Hieke M, Kumar GS, Lewis GR, Gonzalez-Dewhitt KR, Kessler RP, Stein BJ, Hessenberger M, Nairn AC, Peti W, Page R. Understanding the antagonism of retinoblastoma protein dephosphorylation by PNUTS provides insights into the PP1 regulatory code. Proc Natl Acad Sci U S A. 2014 Mar 3. PMID:24591642 doi:http://dx.doi.org/10.1073/pnas.1317395111

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/4mp0"

@@ Line 1: / Line 1: @@
 ==Structure of a second nuclear PP1 Holoenzyme, crystal form 2==
 <StructureSection load='4mp0' size='340' side='right' caption='[[4mp0]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PPP1CA, PPP1A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), Ppp1r10, Cat53, Pnuts ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=4mp0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mp0 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4mp0 RCSB], [http://www.ebi.ac.uk/pdbsum/4mp0 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=4mp0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4mp0 OCA], [http://pdbe.org/4mp0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4mp0 RCSB], [http://www.ebi.ac.uk/pdbsum/4mp0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4mp0 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 4mp0" style="background-color:#fffaf0;"></div>
 ==See Also==

4mp0

From Proteopedia

Revision as of 23:53, 4 August 2016

Structure of a second nuclear PP1 Holoenzyme, crystal form 2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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