6zef: Difference between revisions
New page: '''Unreleased structure''' The entry 6zef is ON HOLD Authors: Mouilleron, S., Treisman, R., Fedoryshchak, R., Lee, R., Butler, A.M., Prechova, M. Description: Structure of PP1(7-300) b... |
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The | ==Structure of PP1(7-300) bound to Phactr1 (516-580) at pH 5.25== | ||
<StructureSection load='6zef' size='340' side='right'caption='[[6zef]], [[Resolution|resolution]] 1.94Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6zef]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ZEF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ZEF FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.94Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=MN:MANGANESE+(II)+ION'>MN</scene></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=6zef FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6zef OCA], [https://pdbe.org/6zef PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6zef RCSB], [https://www.ebi.ac.uk/pdbsum/6zef PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6zef ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/PP1A_HUMAN 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.<ref>PMID:17283141</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
PPP-family phosphatases such as PP1 have little intrinsic specificity. Cofactors can target PP1 to substrates or subcellular locations, but it remains unclear how they might confer sequence-specificity on PP1. The cytoskeletal regulator Phactr1 is a neuronally-enriched PP1 cofactor that is controlled by G-actin. Structural analysis showed that Phactr1 binding remodels PP1's hydrophobic groove, creating a new composite surface adjacent to the catalytic site. Using phosphoproteomics, we identified mouse fibroblast and neuronal Phactr1/PP1 substrates, which include cytoskeletal components and regulators. We determined high-resolution structures of Phactr1/PP1 bound to the dephosphorylated forms of its substrates IRSp53 and spectrin aII. Inversion of the phosphate in these holoenzyme-product complexes supports the proposed PPP-family catalytic mechanism. Substrate sequences C-terminal to the dephosphorylation site make intimate contacts with the composite Phactr1/PP1 surface, which are required for efficient dephosphorylation. Sequence specificity explains why Phactr1/PP1 exhibits orders-of-magnitude enhanced reactivity towards its substrates, compared to apo-PP1 or other PP1 holoenzymes. | |||
Molecular basis for substrate specificity of the Phactr1/PP1 phosphatase holoenzyme.,Fedoryshchak RO, Prechova M, Butler A, Lee R, O'Reilly N, Flynn HR, Snijders AP, Eder N, Ultanir S, Mouilleron S, Treisman R Elife. 2020 Sep 25;9. pii: 61509. doi: 10.7554/eLife.61509. PMID:32975518<ref>PMID:32975518</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 6zef" style="background-color:#fffaf0;"></div> | ||
[[Category: | |||
[[Category: Lee | ==See Also== | ||
[[Category: | *[[Protein phosphatase 3D structures|Protein phosphatase 3D structures]] | ||
[[Category: | == References == | ||
[[Category: | <references/> | ||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Butler AM]] | |||
[[Category: Fedoryshchak R]] | |||
[[Category: Lee R]] | |||
[[Category: Mouilleron S]] | |||
[[Category: Prechova M]] | |||
[[Category: Treisman R]] | |||
Latest revision as of 16:47, 24 January 2024
Structure of PP1(7-300) bound to Phactr1 (516-580) at pH 5.25Structure of PP1(7-300) bound to Phactr1 (516-580) at pH 5.25
Structural highlights
FunctionPP1A_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] Publication Abstract from PubMedPPP-family phosphatases such as PP1 have little intrinsic specificity. Cofactors can target PP1 to substrates or subcellular locations, but it remains unclear how they might confer sequence-specificity on PP1. The cytoskeletal regulator Phactr1 is a neuronally-enriched PP1 cofactor that is controlled by G-actin. Structural analysis showed that Phactr1 binding remodels PP1's hydrophobic groove, creating a new composite surface adjacent to the catalytic site. Using phosphoproteomics, we identified mouse fibroblast and neuronal Phactr1/PP1 substrates, which include cytoskeletal components and regulators. We determined high-resolution structures of Phactr1/PP1 bound to the dephosphorylated forms of its substrates IRSp53 and spectrin aII. Inversion of the phosphate in these holoenzyme-product complexes supports the proposed PPP-family catalytic mechanism. Substrate sequences C-terminal to the dephosphorylation site make intimate contacts with the composite Phactr1/PP1 surface, which are required for efficient dephosphorylation. Sequence specificity explains why Phactr1/PP1 exhibits orders-of-magnitude enhanced reactivity towards its substrates, compared to apo-PP1 or other PP1 holoenzymes. Molecular basis for substrate specificity of the Phactr1/PP1 phosphatase holoenzyme.,Fedoryshchak RO, Prechova M, Butler A, Lee R, O'Reilly N, Flynn HR, Snijders AP, Eder N, Ultanir S, Mouilleron S, Treisman R Elife. 2020 Sep 25;9. pii: 61509. doi: 10.7554/eLife.61509. PMID:32975518[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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