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2xnf

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The Mediator Med25 activator interaction domain: Structure and cooperative binding of VP16 subdomains

Structural highlights

2xnf is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Solution NMR
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

MED25_HUMAN Charcot-Marie-Tooth disease type 2B2. The disease is caused by mutations affecting the gene represented in this entry.^[1]

Function

MED25_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 RARA/RXRA-mediated transcription.^[2] ^[3] ^[4]

Publication Abstract from PubMed

Eukaryotic transcription is regulated by interactions between gene-specific activators and the coactivator complex Mediator. Here we report the NMR structure of the Mediator subunit Med25 (also called Arc92) activator interaction domain (ACID) and analyze the structural and functional interaction of ACID with the archetypical acidic transcription activator VP16. Unlike other known activator targets, ACID forms a seven-stranded beta-barrel framed by three helices. The VP16 subdomains H1 and H2 bind to opposite faces of ACID and cooperate during promoter-dependent activated transcription in a in vitro system. The activator-binding ACID faces are functionally required and conserved among higher eukaryotes. Comparison with published activator structures reveals that the VP16 activation domain uses distinct interaction modes to adapt to unrelated target surfaces and folds that evolved for activator binding.

Structure and VP16 binding of the Mediator Med25 activator interaction domain.,Vojnic E, Mourao A, Seizl M, Simon B, Wenzeck L, Lariviere L, Baumli S, Baumgart K, Meisterernst M, Sattler M, Cramer P Nat Struct Mol Biol. 2011 Apr;18(4):404-9. Epub 2011 Mar 6. PMID:21378965^[5]

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

References

↑ Leal A, Huehne K, Bauer F, Sticht H, Berger P, Suter U, Morera B, Del Valle G, Lupski JR, Ekici A, Pasutto F, Endele S, Barrantes R, Berghoff C, Berghoff M, Neundorfer B, Heuss D, Dorn T, Young P, Santolin L, Uhlmann T, Meisterernst M, Sereda MW, Stassart RM, Meyer zu Horste G, Nave KA, Reis A, Rautenstrauss B. Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal models. Neurogenetics. 2009 Oct;10(4):275-87. doi: 10.1007/s10048-009-0183-3. Epub 2009, Mar 17. PMID:19290556 doi:http://dx.doi.org/10.1007/s10048-009-0183-3
↑ Mittler G, Stuhler T, Santolin L, Uhlmann T, Kremmer E, Lottspeich F, Berti L, Meisterernst M. A novel docking site on Mediator is critical for activation by VP16 in mammalian cells. EMBO J. 2003 Dec 15;22(24):6494-504. PMID:14657022 doi:http://dx.doi.org/10.1093/emboj/cdg619
↑ Yang F, DeBeaumont R, Zhou S, Naar AM. The activator-recruited cofactor/Mediator coactivator subunit ARC92 is a functionally important target of the VP16 transcriptional activator. Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2339-44. PMID:14983011
↑ Lee HK, Park UH, Kim EJ, Um SJ. MED25 is distinct from TRAP220/MED1 in cooperating with CBP for retinoid receptor activation. EMBO J. 2007 Aug 8;26(15):3545-57. Epub 2007 Jul 19. PMID:17641689 doi:http://dx.doi.org/7601797
↑ Vojnic E, Mourao A, Seizl M, Simon B, Wenzeck L, Lariviere L, Baumli S, Baumgart K, Meisterernst M, Sattler M, Cramer P. Structure and VP16 binding of the Mediator Med25 activator interaction domain. Nat Struct Mol Biol. 2011 Apr;18(4):404-9. Epub 2011 Mar 6. PMID:21378965 doi:10.1038/nsmb.1997

1 Structural highlights
2 Disease
3 Function
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/2xnf"

@@ Line 1: / Line 1: @@
-==THE MEDIATOR MED25 ACTIVATOR INTERACTION DOMAIN: STRUCTURE AND COOPERATIVE BINDING OF VP16 SUBDOMAINS==
+==The Mediator Med25 activator interaction domain: Structure and cooperative binding of VP16 subdomains==
-<StructureSection load='2xnf' size='340' side='right' caption='[[2xnf]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''>
+<StructureSection load='2xnf' size='340' side='right'caption='[[2xnf]]' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[2xnf]] 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=2XNF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2XNF FirstGlance]. <br>
+<table><tr><td colspan='2'>[[2xnf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2XNF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2XNF FirstGlance]. <br>
-</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=2xnf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xnf OCA], [http://pdbe.org/2xnf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2xnf RCSB], [http://www.ebi.ac.uk/pdbsum/2xnf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2xnf ProSAT]</span></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2xnf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2xnf OCA], [https://pdbe.org/2xnf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2xnf RCSB], [https://www.ebi.ac.uk/pdbsum/2xnf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2xnf ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/MED25_HUMAN MED25_HUMAN]] Charcot-Marie-Tooth disease type 2B2. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:19290556</ref>
+[https://www.uniprot.org/uniprot/MED25_HUMAN MED25_HUMAN] Charcot-Marie-Tooth disease type 2B2. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:19290556</ref>
 == Function ==
-[[http://www.uniprot.org/uniprot/MED25_HUMAN MED25_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 RARA/RXRA-mediated transcription.<ref>PMID:14657022</ref> <ref>PMID:14983011</ref> <ref>PMID:17641689</ref>
+[https://www.uniprot.org/uniprot/MED25_HUMAN MED25_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 RARA/RXRA-mediated transcription.<ref>PMID:14657022</ref> <ref>PMID:14983011</ref> <ref>PMID:17641689</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 26: / Line 27: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
-[[Category: Baumli, S]]
+[[Category: Large Structures]]
-[[Category: Cramer, P]]
+[[Category: Baumli S]]
-[[Category: Lariviere, L]]
+[[Category: Cramer P]]
-[[Category: Meisterernst, M]]
+[[Category: Lariviere L]]
-[[Category: Mourao, A]]
+[[Category: Meisterernst M]]
-[[Category: Sattler, M]]
+[[Category: Mourao A]]
-[[Category: Seizl, M]]
+[[Category: Sattler M]]
-[[Category: Simon, B]]
+[[Category: Seizl M]]
-[[Category: Vojnic, E]]
+[[Category: Simon B]]
-[[Category: Wenzeck, L]]
+[[Category: Vojnic E]]
-[[Category: Activated transcription]]
+[[Category: Wenzeck L]]
-[[Category: Mediator]]
-[[Category: Transcription]]

2xnf

From Proteopedia

Current revision

The Mediator Med25 activator interaction domain: Structure and cooperative binding of VP16 subdomains

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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