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2gut

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Revision as of 07:24, 17 March 2021

Solution structure of the trans-activation domain of the human co-activator ARC105

Structural highlights

2gut is a 1 chain structure with sequence from Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Gene:	PCQAP, ARC105, CTG7A, TIG1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[MED15_HUMAN] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Required for cholesterol-dependent gene regulation. Positively regulates the Nodal signaling pathway.^[1] ^[2] ^[3]

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

The sterol regulatory element binding protein (SREBP) family of transcription activators are critical regulators of cholesterol and fatty acid homeostasis. We previously demonstrated that human SREBPs bind the CREB-binding protein (CBP)/p300 acetyltransferase KIX domain and recruit activator-recruited co-factor (ARC)/Mediator co-activator complexes through unknown mechanisms. Here we show that SREBPs use the evolutionarily conserved ARC105 (also called MED15) subunit to activate target genes. Structural analysis of the SREBP-binding domain in ARC105 by NMR revealed a three-helix bundle with marked similarity to the CBP/p300 KIX domain. In contrast to SREBPs, the CREB and c-Myb activators do not bind the ARC105 KIX domain, although they interact with the CBP KIX domain, revealing a surprising specificity among structurally related activator-binding domains. The Caenorhabditis elegans SREBP homologue SBP-1 promotes fatty acid homeostasis by regulating the expression of lipogenic enzymes. We found that, like SBP-1, the C. elegans ARC105 homologue MDT-15 is required for fatty acid homeostasis, and show that both SBP-1 and MDT-15 control transcription of genes governing desaturation of stearic acid to oleic acid. Notably, dietary addition of oleic acid significantly rescued various defects of nematodes targeted with RNA interference against sbp-1 and mdt-15, including impaired intestinal fat storage, infertility, decreased size and slow locomotion, suggesting that regulation of oleic acid levels represents a physiologically critical function of SBP-1 and MDT-15. Taken together, our findings demonstrate that ARC105 is a key effector of SREBP-dependent gene regulation and control of lipid homeostasis in metazoans.

An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis.,Yang F, Vought BW, Satterlee JS, Walker AK, Jim Sun ZY, Watts JL, DeBeaumont R, Saito RM, Hyberts SG, Yang S, Macol C, Iyer L, Tjian R, van den Heuvel S, Hart AC, Wagner G, Naar AM Nature. 2006 Aug 10;442(7103):700-4. Epub 2006 Jun 21. PMID:16799563^[4]

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

References

↑ Kato Y, Habas R, Katsuyama Y, Naar AM, He X. A component of the ARC/Mediator complex required for TGF beta/Nodal signalling. Nature. 2002 Aug 8;418(6898):641-6. Epub 2002 Jul 24. PMID:12167862 doi:http://dx.doi.org/10.1038/nature00969
↑ Andrau JC, van de Pasch L, Lijnzaad P, Bijma T, Koerkamp MG, van de Peppel J, Werner M, Holstege FC. Genome-wide location of the coactivator mediator: Binding without activation and transient Cdk8 interaction on DNA. Mol Cell. 2006 Apr 21;22(2):179-92. PMID:16630888 doi:http://dx.doi.org/S1097-2765(06)00189-4
↑ Yang F, Vought BW, Satterlee JS, Walker AK, Jim Sun ZY, Watts JL, DeBeaumont R, Saito RM, Hyberts SG, Yang S, Macol C, Iyer L, Tjian R, van den Heuvel S, Hart AC, Wagner G, Naar AM. An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. Nature. 2006 Aug 10;442(7103):700-4. Epub 2006 Jun 21. PMID:16799563 doi:10.1038/nature04942
↑ Yang F, Vought BW, Satterlee JS, Walker AK, Jim Sun ZY, Watts JL, DeBeaumont R, Saito RM, Hyberts SG, Yang S, Macol C, Iyer L, Tjian R, van den Heuvel S, Hart AC, Wagner G, Naar AM. An ARC/Mediator subunit required for SREBP control of cholesterol and lipid homeostasis. Nature. 2006 Aug 10;442(7103):700-4. Epub 2006 Jun 21. PMID:16799563 doi:10.1038/nature04942

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==Solution structure of the trans-activation domain of the human co-activator ARC105==
-<StructureSection load='2gut' size='340' side='right' caption='[[2gut]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''>
+<StructureSection load='2gut' size='340' side='right'caption='[[2gut]], [[NMR_Ensembles_of_Models | 15 NMR models]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2gut]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GUT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2GUT FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2gut]] is a 1 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=2GUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GUT FirstGlance]. <br>
-</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PCQAP, ARC105, CTG7A, TIG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+</td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PCQAP, ARC105, CTG7A, TIG1 ([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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gut OCA], [http://pdbe.org/2gut PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2gut RCSB], [http://www.ebi.ac.uk/pdbsum/2gut PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2gut 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=2gut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gut OCA], [https://pdbe.org/2gut PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gut RCSB], [https://www.ebi.ac.uk/pdbsum/2gut PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gut ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/MED15_HUMAN MED15_HUMAN]] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Required for cholesterol-dependent gene regulation. Positively regulates the Nodal signaling pathway.<ref>PMID:12167862</ref> <ref>PMID:16630888</ref> <ref>PMID:16799563</ref>
+[[https://www.uniprot.org/uniprot/MED15_HUMAN MED15_HUMAN]] Component of the Mediator complex, a coactivator involved in the regulated transcription of nearly all RNA polymerase II-dependent genes. Mediator functions as a bridge to convey information from gene-specific regulatory proteins to the basal RNA polymerase II transcription machinery. Mediator is recruited to promoters by direct interactions with regulatory proteins and serves as a scaffold for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. Required for cholesterol-dependent gene regulation. Positively regulates the Nodal signaling pathway.<ref>PMID:12167862</ref> <ref>PMID:16630888</ref> <ref>PMID:16799563</ref>
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 33: / Line 33: @@
 </StructureSection>
 [[Category: Human]]
+[[Category: Large Structures]]
 [[Category: Hyberts, S G]]
 [[Category: Naar, A M]]

2gut

From Proteopedia

Revision as of 07:24, 17 March 2021

Solution structure of the trans-activation domain of the human co-activator ARC105

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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