2rt5

From Proteopedia

(Difference between revisions)

Revision as of 04:55, 25 August 2022

Structural insights into the recruitment of SMRT by the co-repressor SHARP under phosphorylative regulation

Structural highlights

2rt5 is a 2 chain structure. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
NonStd Res:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MINT_HUMAN] May serve as a nuclear matrix platform that organizes and integrates transcriptional responses. In osteoblasts, supports transcription activation: synergizes with RUNX2 to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) (By similarity). Has also been shown to be an essential corepressor protein, which probably regulates different key pathways such as the Notch pathway. Negative regulator of the Notch pathway via its interaction with RBPSUH, which prevents the association between NOTCH1 and RBPSUH, and therefore suppresses the transactivation activity of Notch signaling. Blocks the differentiation of precursor B-cells into marginal zone B-cells. Probably represses transcription via the recruitment of large complexes containing histone deacetylase proteins. May bind both to DNA and RNA.^[1] ^[2] [NCOR2_HUMAN] Transcriptional corepressor of NR4A2/NURR1 and acts through histone deacetylases (HDACs) to keep promoters of NR4A2/NURR1 target genes in a repressed deacetylated state (By similarity). Mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription. Isoform 1 and isoform 5 have different affinities for different nuclear receptors.

Publication Abstract from PubMed

The transcriptional corepressors SMRT/NCoR, components of histone deacetylase complexes, interact with nuclear receptors and many other transcription factors. SMRT is a target for the ubiquitously expressed protein kinase CK2, which is known to phosphorylate a wide variety of substrates. Increasing evidence suggests that CK2 plays a regulatory role in many cellular events, particularly, in transcription. However, little is known about the precise mode of action involved. Here, we report the three-dimensional structure of a SMRT/HDAC1-associated repressor protein (SHARP) in complex with phosphorylated SMRT, as determined by solution NMR. Phosphorylation of the CK2 site on SMRT significantly increased affinity for SHARP. We also confirmed the significance of CK2 phosphorylation by reporter assay and propose a mechanism involving the process of phosphorylation acting as a molecular switch. Finally, we propose that the SPOC domain functions as a phosphorylation binding module.

Structural Insights into the Recruitment of SMRT by the Corepressor SHARP under Phosphorylative Regulation.,Mikami S, Kanaba T, Takizawa N, Kobayashi A, Maesaki R, Fujiwara T, Ito Y, Mishima M Structure. 2013 Nov 19. pii: S0969-2126(13)00400-0. doi:, 10.1016/j.str.2013.10.007. PMID:24268649^[3]

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

References

↑ Shi Y, Downes M, Xie W, Kao HY, Ordentlich P, Tsai CC, Hon M, Evans RM. Sharp, an inducible cofactor that integrates nuclear receptor repression and activation. Genes Dev. 2001 May 1;15(9):1140-51. PMID:11331609 doi:http://dx.doi.org/10.1101/gad.871201
↑ Oswald F, Kostezka U, Astrahantseff K, Bourteele S, Dillinger K, Zechner U, Ludwig L, Wilda M, Hameister H, Knochel W, Liptay S, Schmid RM. SHARP is a novel component of the Notch/RBP-Jkappa signalling pathway. EMBO J. 2002 Oct 15;21(20):5417-26. PMID:12374742
↑ Mikami S, Kanaba T, Takizawa N, Kobayashi A, Maesaki R, Fujiwara T, Ito Y, Mishima M. Structural Insights into the Recruitment of SMRT by the Corepressor SHARP under Phosphorylative Regulation. Structure. 2013 Nov 19. pii: S0969-2126(13)00400-0. doi:, 10.1016/j.str.2013.10.007. PMID:24268649 doi:http://dx.doi.org/10.1016/j.str.2013.10.007

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2rt5"

@@ Line 3: / Line 3: @@
 <StructureSection load='2rt5' size='340' side='right'caption='[[2rt5]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2rt5]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RT5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RT5 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2rt5]] is a 2 chain structure. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2RT5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2RT5 FirstGlance]. <br>
 </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SEP:PHOSPHOSERINE'>SEP</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">SHARP ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2rt5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2rt5 OCA], [https://pdbe.org/2rt5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2rt5 RCSB], [https://www.ebi.ac.uk/pdbsum/2rt5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2rt5 ProSAT]</span></td></tr>
 </table>
@@ Line 23: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Kanaba, T]]

2rt5

From Proteopedia

Revision as of 04:55, 25 August 2022

Structural insights into the recruitment of SMRT by the co-repressor SHARP under phosphorylative regulation

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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