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==HUMAN MED26 N-TERMINAL DOMAIN (1-92)== | |||
<StructureSection load='5odd' size='340' side='right' caption='[[5odd]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[5odd]] is a 1 chain structure. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=2mzo 2mzo]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ODD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ODD 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=5odd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5odd OCA], [http://pdbe.org/5odd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5odd RCSB], [http://www.ebi.ac.uk/pdbsum/5odd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5odd ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[http://www.uniprot.org/uniprot/MED26_HUMAN MED26_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 pre-initiation complex with RNA polymerase II and the general transcription factors. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
MED26 is a subunit of Mediator, a large complex central to the regulation of gene transcription by RNA Polymerase II. MED26 plays a role in the switch between the initiation and elongation phases of RNA Polymerase II-mediated transcription process. Regulation of these steps requires successive binding of MED26 N-terminal domain (NTD) to TATA-binding protein-associated factor 7 (TAF7) and Eleven-nineteen lysine-rich in leukemia-Associated Factor 1 (EAF1). In order to investigate the mechanism of regulation by MED26, MED26-NTD structure was solved by NMR, revealing a 4-helix bundle. EAF1 (239-268) and TAF7 (205-235) peptide interactions were both mapped to the same groove formed by H3 and H4 helices of MED26-NTD. Both interactions are characterized by dissociation constants in the 10-muM range. Further experiments revealed a folding-upon-binding mechanism that leads to the formation of EAF1 (N247-S260) and TAF7 (L214-S227) helices. Chemical shift perturbations and nuclear Overhauser enhancement contacts support the involvement of residues I222/F223 in anchoring TAF7 helix to a hydrophobic pocket of MED26-NTD, including residues L48, W80 and I84. In addition, Ala mutations of charged residues located in the C-terminal disordered part of TAF7 and EAF1 peptides affected the binding, with a loss of affinity characterized by a 10-time increase of dissociation constants. A structural model of MED26-NTD/TAF7 complex shows bi-partite components, combining ordered and disordered segments, as well as hydrophobic and electrostatic contributions to the binding. This study provides molecular detail that will help to decipher the mechanistic basis for the initiation to elongation switch-function mediated by MED26-NTD. | |||
Solution Structure of the N-Terminal Domain of Mediator Subunit MED26 and Molecular Characterization of Its Interaction with EAF1 and TAF7.,Lens Z, Cantrelle FX, Peruzzini R, Hanoulle X, Dewitte F, Ferreira E, Baert JL, Monte D, Aumercier M, Villeret V, Verger A, Landrieu I J Mol Biol. 2017 Oct 13;429(20):3043-3055. doi: 10.1016/j.jmb.2017.09.001. Epub, 2017 Sep 9. PMID:28893534<ref>PMID:28893534</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 5odd" style="background-color:#fffaf0;"></div> | ||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Cantrelle, F X]] | |||
[[Category: Dewitte, F]] | |||
[[Category: Hanoulle, X]] | |||
[[Category: Landrieu, I]] | |||
[[Category: Lens, Z]] | [[Category: Lens, Z]] | ||
[[Category: Perruzini, R]] | [[Category: Perruzini, R]] | ||
[[Category: | [[Category: Verger, A]] | ||
[[Category: Villeret, V]] | [[Category: Villeret, V]] | ||
[[Category: | [[Category: Mediator complex transcriptional regulation]] | ||
[[Category: Transcription]] | |||