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| | ==Solution structure of yeast Med15 ABD2 residues 277-368== | | ==Solution structure of yeast Med15 ABD2 residues 277-368== |
| - | <StructureSection load='6aly' size='340' side='right'caption='[[6aly]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='6aly' size='340' side='right'caption='[[6aly]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6aly]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ALY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6ALY FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6aly]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6ALY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6ALY 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=6aly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aly OCA], [http://pdbe.org/6aly PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6aly RCSB], [http://www.ebi.ac.uk/pdbsum/6aly PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6aly ProSAT]</span></td></tr> | + | </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=6aly FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6aly OCA], [https://pdbe.org/6aly PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6aly RCSB], [https://www.ebi.ac.uk/pdbsum/6aly PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6aly ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MED15_YEAST MED15_YEAST]] 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. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins. It has an important role in the negative regulation of Ty transcription.<ref>PMID:16076843</ref> <ref>PMID:16109375</ref> <ref>PMID:16263706</ref> | + | [https://www.uniprot.org/uniprot/MED15_YEAST MED15_YEAST] 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. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins. It has an important role in the negative regulation of Ty transcription.<ref>PMID:16076843</ref> <ref>PMID:16109375</ref> <ref>PMID:16263706</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 18824]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Hahn, S]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Klevit, R E]] | + | [[Category: Hahn S]] |
| - | [[Category: Pacheco, D]] | + | [[Category: Klevit RE]] |
| - | [[Category: Tuttle, L M]] | + | [[Category: Pacheco D]] |
| - | [[Category: Warfield, L]] | + | [[Category: Tuttle LM]] |
| - | [[Category: Abd]]
| + | [[Category: Warfield L]] |
| - | [[Category: Gal11]]
| + | |
| - | [[Category: Helical]]
| + | |
| - | [[Category: Med15]]
| + | |
| - | [[Category: Mediator]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription activation]]
| + | |
| - | [[Category: Yeast]]
| + | |
| Structural highlights
Function
MED15_YEAST 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. The Mediator complex, having a compact conformation in its free form, is recruited to promoters by direct interactions with regulatory proteins and serves for the assembly of a functional preinitiation complex with RNA polymerase II and the general transcription factors. The Mediator complex unfolds to an extended conformation and partially surrounds RNA polymerase II, specifically interacting with the unphosphorylated form of the C-terminal domain (CTD) of RNA polymerase II. The Mediator complex dissociates from the RNA polymerase II holoenzyme and stays at the promoter when transcriptional elongation begins. It has an important role in the negative regulation of Ty transcription.[1] [2] [3]
Publication Abstract from PubMed
Transcription activation domains (ADs) are inherently disordered proteins that often target multiple coactivator complexes, but the specificity of these interactions is not understood. Efficient transcription activation by yeast Gcn4 requires its tandem ADs and four activator-binding domains (ABDs) on its target, the Mediator subunit Med15. Multiple ABDs are a common feature of coactivator complexes. We find that the large Gcn4-Med15 complex is heterogeneous and contains nearly all possible AD-ABD interactions. Gcn4-Med15 forms via a dynamic fuzzy protein-protein interface, where ADs bind the ABDs in multiple orientations via hydrophobic regions that gain helicity. This combinatorial mechanism allows individual low-affinity and specificity interactions to generate a biologically functional, specific, and higher affinity complex despite lacking a defined protein-protein interface. This binding strategy is likely representative of many activators that target multiple coactivators, as it allows great flexibility in combinations of activators that can cooperate to regulate genes with variable coactivator requirements.
Gcn4-Mediator Specificity Is Mediated by a Large and Dynamic Fuzzy Protein-Protein Complex.,Tuttle LM, Pacheco D, Warfield L, Luo J, Ranish J, Hahn S, Klevit RE Cell Rep. 2018 Mar 20;22(12):3251-3264. doi: 10.1016/j.celrep.2018.02.097. PMID:29562181[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nair D, Kim Y, Myers LC. Mediator and TFIIH govern carboxyl-terminal domain-dependent transcription in yeast extracts. J Biol Chem. 2005 Oct 7;280(40):33739-48. Epub 2005 Aug 2. PMID:16076843 doi:http://dx.doi.org/M506067200
- ↑ van de Peppel J, Kettelarij N, van Bakel H, Kockelkorn TT, van Leenen D, Holstege FC. Mediator expression profiling epistasis reveals a signal transduction pathway with antagonistic submodules and highly specific downstream targets. Mol Cell. 2005 Aug 19;19(4):511-22. PMID:16109375 doi:http://dx.doi.org/10.1016/j.molcel.2005.06.033
- ↑ Takagi Y, Kornberg RD. Mediator as a general transcription factor. J Biol Chem. 2006 Jan 6;281(1):80-9. Epub 2005 Nov 1. PMID:16263706 doi:http://dx.doi.org/M508253200
- ↑ Tuttle LM, Pacheco D, Warfield L, Luo J, Ranish J, Hahn S, Klevit RE. Gcn4-Mediator Specificity Is Mediated by a Large and Dynamic Fuzzy Protein-Protein Complex. Cell Rep. 2018 Mar 20;22(12):3251-3264. doi: 10.1016/j.celrep.2018.02.097. PMID:29562181 doi:http://dx.doi.org/10.1016/j.celrep.2018.02.097
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