2ght

From Proteopedia

(Difference between revisions)

Current revision

CTD-specific phosphatase Scp1 in complex with peptide from C-terminal domain of RNA polymerase II

Structural highlights

2ght is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.8Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

CTDS1_HUMAN Preferentially catalyzes the dephosphorylation of 'Ser-5' within the tandem 7 residues repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Phosphorylation and dephosphorylation of the C-terminal domain (CTD) of RNA polymerase II (Pol II) represent a critical regulatory checkpoint for transcription. Transcription initiation requires Fcp1/Scp1-mediated dephosphorylation of phospho-CTD. Fcp1 and Scp1 belong to a family of Mg2+ -dependent phosphoserine (P.Ser)/phosphothreonine (P.Thr)-specific phosphatases. We recently showed that Scp1 is an evolutionarily conserved regulator of neuronal gene silencing. Here, we present the X-ray crystal structures of a dominant-negative form of human Scp1 (D96N mutant) bound to mono- and diphosphorylated peptides encompassing the CTD heptad repeat (Y1S2P3T4S5P6S7). Moreover, kinetic and thermodynamic analyses of Scp1-phospho-CTD peptide complexes support the structures determined. This combined structure-function analysis discloses the residues in Scp1 involved in CTD binding and its preferential dephosphorylation of P.Ser5 of the CTD heptad repeat. Moreover, these results provide a template for the design of specific inhibitors of Scp1 for the study of neuronal stem cell development.

Determinants for dephosphorylation of the RNA polymerase II C-terminal domain by Scp1.,Zhang Y, Kim Y, Genoud N, Gao J, Kelly JW, Pfaff SL, Gill GN, Dixon JE, Noel JP Mol Cell. 2006 Dec 8;24(5):759-70. PMID:17157258^[3]

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

References

↑ Yeo M, Lin PS, Dahmus ME, Gill GN. A novel RNA polymerase II C-terminal domain phosphatase that preferentially dephosphorylates serine 5. J Biol Chem. 2003 Jul 11;278(28):26078-85. Epub 2003 Apr 28. PMID:12721286 doi:10.1074/jbc.M301791200
↑ Yeo M, Lee SK, Lee B, Ruiz EC, Pfaff SL, Gill GN. Small CTD phosphatases function in silencing neuronal gene expression. Science. 2005 Jan 28;307(5709):596-600. PMID:15681389 doi:10.1126/science.1100801
↑ Zhang Y, Kim Y, Genoud N, Gao J, Kelly JW, Pfaff SL, Gill GN, Dixon JE, Noel JP. Determinants for dephosphorylation of the RNA polymerase II C-terminal domain by Scp1. Mol Cell. 2006 Dec 8;24(5):759-70. PMID:17157258 doi:10.1016/j.molcel.2006.10.027

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ght"

Categories: Homo sapiens | Large Structures | Noel JP | Zhang Y

@@ Line 1: / Line 1: @@
-{{Seed}}
-[[Image:2ght.png|left|200px]]
-<!--
+==CTD-specific phosphatase Scp1 in complex with peptide from C-terminal domain of RNA polymerase II==
-The line below this paragraph, containing "STRUCTURE_2ght", creates the "Structure Box" on the page.
+<StructureSection load='2ght' size='340' side='right'caption='[[2ght]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[2ght]] 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=2GHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GHT FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.8&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-{{STRUCTURE_2ght|  PDB=2ght  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2ght FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ght OCA], [https://pdbe.org/2ght PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2ght RCSB], [https://www.ebi.ac.uk/pdbsum/2ght PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2ght ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/CTDS1_HUMAN CTDS1_HUMAN] Preferentially catalyzes the dephosphorylation of 'Ser-5' within the tandem 7 residues repeats in the C-terminal domain (CTD) of the largest RNA polymerase II subunit POLR2A. Negatively regulates RNA polymerase II transcription, possibly by controlling the transition from initiation/capping to processive transcript elongation. Recruited by REST to neuronal genes that contain RE-1 elements, leading to neuronal gene silencing in non-neuronal cells.<ref>PMID:12721286</ref> <ref>PMID:15681389</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gh/2ght_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2ght ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Phosphorylation and dephosphorylation of the C-terminal domain (CTD) of RNA polymerase II (Pol II) represent a critical regulatory checkpoint for transcription. Transcription initiation requires Fcp1/Scp1-mediated dephosphorylation of phospho-CTD. Fcp1 and Scp1 belong to a family of Mg2+ -dependent phosphoserine (P.Ser)/phosphothreonine (P.Thr)-specific phosphatases. We recently showed that Scp1 is an evolutionarily conserved regulator of neuronal gene silencing. Here, we present the X-ray crystal structures of a dominant-negative form of human Scp1 (D96N mutant) bound to mono- and diphosphorylated peptides encompassing the CTD heptad repeat (Y1S2P3T4S5P6S7). Moreover, kinetic and thermodynamic analyses of Scp1-phospho-CTD peptide complexes support the structures determined. This combined structure-function analysis discloses the residues in Scp1 involved in CTD binding and its preferential dephosphorylation of P.Ser5 of the CTD heptad repeat. Moreover, these results provide a template for the design of specific inhibitors of Scp1 for the study of neuronal stem cell development.
-===CTD-specific phosphatase Scp1 in complex with peptide from C-terminal domain of RNA polymerase II===
+Determinants for dephosphorylation of the RNA polymerase II C-terminal domain by Scp1.,Zhang Y, Kim Y, Genoud N, Gao J, Kelly JW, Pfaff SL, Gill GN, Dixon JE, Noel JP Mol Cell. 2006 Dec 8;24(5):759-70. PMID:17157258<ref>PMID:17157258</ref>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
+<div class="pdbe-citations 2ght" style="background-color:#fffaf0;"></div>
-<!--
+==See Also==
-The line below this paragraph, {{ABSTRACT_PUBMED_17157258}}, adds the Publication Abstract to the page
+*[[RNA polymerase 3D structures|RNA polymerase 3D structures]]
-(as it appears on PubMed at http://www.pubmed.gov), where 17157258 is the PubMed ID number.
+== References ==
--->
+<references/>
-{{ABSTRACT_PUBMED_17157258}}
+__TOC__
+</StructureSection>
-==About this Structure==
-GHT is a 4 chains structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GHT OCA].
-==Reference==
-<ref group="xtra">PMID:17157258</ref><references group="xtra"/>
 [[Category: Homo sapiens]]
-[[Category: Phosphoprotein phosphatase]]
+[[Category: Large Structures]]
-[[Category: Noel, J P.]]
+[[Category: Noel JP]]
-[[Category: Zhang, Y.]]
+[[Category: Zhang Y]]
-[[Category: Had superfamily]]
-[[Category: Protein-peptide complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Feb 16 11:39:45 2009''

2ght

From Proteopedia

Current revision

CTD-specific phosphatase Scp1 in complex with peptide from C-terminal domain of RNA polymerase II

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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