|
|
| Line 3: |
Line 3: |
| | <StructureSection load='5zt0' size='340' side='right'caption='[[5zt0]], [[Resolution|resolution]] 3.32Å' scene=''> | | <StructureSection load='5zt0' size='340' side='right'caption='[[5zt0]], [[Resolution|resolution]] 3.32Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5zt0]] is a 10 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZT0 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZT0 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5zt0]] is a 10 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZT0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5ZT0 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3204267Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=5zt0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zt0 OCA], [http://pdbe.org/5zt0 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zt0 RCSB], [http://www.ebi.ac.uk/pdbsum/5zt0 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zt0 ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5zt0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zt0 OCA], [https://pdbe.org/5zt0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5zt0 RCSB], [https://www.ebi.ac.uk/pdbsum/5zt0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5zt0 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PP1A_MOUSE PP1A_MOUSE]] 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. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates CENPA (By similarity). Dephosphorylates the 'Ser-139' residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy (By similarity).[UniProtKB:P62136]<ref>PMID:17609112</ref> <ref>PMID:21712997</ref> <ref>PMID:21930935</ref> <ref>PMID:22215812</ref> [[http://www.uniprot.org/uniprot/PPR3B_HUMAN PPR3B_HUMAN]] Acts as a glycogen-targeting subunit for phosphatase PP1. Facilitates interaction of the PP1 with enzymes of the glycogen metabolism and regulates its activity. Suppresses the rate at which PP1 dephosphorylates (inactivates) glycogen phosphorylase and enhances the rate at which it activates glycogen synthase and therefore limits glycogen breakdown. Its activity is inhibited by PYGL, resulting in inhibition of the glycogen synthase and glycogen phosphorylase phosphatase activities of PP1. Dramatically increases basal and insulin-stimulated glycogen synthesis upon overexpression in hepatocytes (By similarity). | + | [https://www.uniprot.org/uniprot/PP1A_MOUSE PP1A_MOUSE] 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. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates CENPA (By similarity). Dephosphorylates the 'Ser-139' residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy (By similarity).[UniProtKB:P62136]<ref>PMID:17609112</ref> <ref>PMID:21712997</ref> <ref>PMID:21930935</ref> <ref>PMID:22215812</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
| Line 19: |
Line 19: |
| | </div> | | </div> |
| | <div class="pdbe-citations 5zt0" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5zt0" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Phosphoprotein phosphatase]] | + | [[Category: Mus musculus]] |
| - | [[Category: Xiang, S]] | + | [[Category: Xiang S]] |
| - | [[Category: Yu, J]] | + | [[Category: Yu J]] |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Protein phosphorylase 1 holoenzyme]]
| + | |
| Structural highlights
Function
PP1A_MOUSE 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. In balance with CSNK1D and CSNK1E, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. May dephosphorylate CSNK1D and CSNK1E. Dephosphorylates CENPA (By similarity). Dephosphorylates the 'Ser-139' residue of ATG16L1 causing dissociation of ATG12-ATG5-ATG16L1 complex, thereby inhibiting autophagy (By similarity).[UniProtKB:P62136][1] [2] [3] [4]
Publication Abstract from PubMed
The rate-limiting enzymes in glycogen metabolism are subject to regulation by reversible phosphorylation. The glycogen-targeted protein phosphatase 1 (PP1) holoenzyme catalyzes their dephosphorylation. It is composed of a catalytic subunit (PP1C) and a glycogen-targeting subunit (G subunit). To date, seven G subunits have been identified. They all contain an RVxF PP1C-binding motif. The interactions between this motif in the skeletal muscle-specific GM and PP1C have been revealed by structural studies. However, whether elements outside of this motif contribute to the interaction with PP1C is not clear. In this study, we found that residues next to the RVxF motif in GM also mediate interactions to PP1C and revealed the mechanism of the interaction by structural studies. Sequence analysis revealed that the PP1C-binding region in GM is highly conserved among G subunits. Consistently, we found that the equivalent region in the liver-enriched GL adopts a similar structure upon binding PP1C. Dephosphorylation experiments indicated that this region and the glycogen-binding region in GM cooperate to stimulate PP1C's activity toward glycogen-associated substrates. DATABASES: The structure factors and coordinates for the PP1Calpha-GM (1-99) and PP1Calpha-GL (31-105) complexes have been deposited into the Protein Data Bank (http://www.pdb.org), with the accession codes 5ZQV and 5ZT0, respectively.
Structural basis for protein phosphatase 1 recruitment by glycogen-targeting subunits.,Yu J, Deng T, Xiang S FEBS J. 2018 Dec;285(24):4646-4659. doi: 10.1111/febs.14699. Epub 2018 Nov 28. PMID:30422398[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Kim TH, Goodman J, Anderson KV, Niswander L. Phactr4 regulates neural tube and optic fissure closure by controlling PP1-, Rb-, and E2F1-regulated cell-cycle progression. Dev Cell. 2007 Jul;13(1):87-102. doi: 10.1016/j.devcel.2007.04.018. PMID:17609112 doi:http://dx.doi.org/10.1016/j.devcel.2007.04.018
- ↑ Schmutz I, Wendt S, Schnell A, Kramer A, Mansuy IM, Albrecht U. Protein phosphatase 1 (PP1) is a post-translational regulator of the mammalian circadian clock. PLoS One. 2011;6(6):e21325. doi: 10.1371/journal.pone.0021325. Epub 2011 Jun 21. PMID:21712997 doi:http://dx.doi.org/10.1371/journal.pone.0021325
- ↑ Lee HM, Chen R, Kim H, Etchegaray JP, Weaver DR, Lee C. The period of the circadian oscillator is primarily determined by the balance between casein kinase 1 and protein phosphatase 1. Proc Natl Acad Sci U S A. 2011 Sep 27;108(39):16451-6. doi:, 10.1073/pnas.1107178108. Epub 2011 Sep 19. PMID:21930935 doi:http://dx.doi.org/10.1073/pnas.1107178108
- ↑ Zhang Y, Kim TH, Niswander L. Phactr4 regulates directional migration of enteric neural crest through PP1, integrin signaling, and cofilin activity. Genes Dev. 2012 Jan 1;26(1):69-81. doi: 10.1101/gad.179283.111. PMID:22215812 doi:http://dx.doi.org/10.1101/gad.179283.111
- ↑ Yu J, Deng T, Xiang S. Structural basis for protein phosphatase 1 recruitment by glycogen-targeting subunits. FEBS J. 2018 Dec;285(24):4646-4659. doi: 10.1111/febs.14699. Epub 2018 Nov 28. PMID:30422398 doi:http://dx.doi.org/10.1111/febs.14699
|
