|
|
| Line 1: |
Line 1: |
| | | | |
| | ==Solution Structure of Yeast Gal11p kix domain== | | ==Solution Structure of Yeast Gal11p kix domain== |
| - | <StructureSection load='2k0n' size='340' side='right'caption='[[2k0n]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2k0n' size='340' side='right'caption='[[2k0n]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2k0n]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2K0N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K0N FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2k0n]] 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=2K0N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2K0N FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GAL11, ABE1, MED15, RAR3, SDS4, SPT13 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</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=2k0n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k0n OCA], [https://pdbe.org/2k0n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k0n RCSB], [https://www.ebi.ac.uk/pdbsum/2k0n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k0n 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=2k0n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2k0n OCA], [https://pdbe.org/2k0n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2k0n RCSB], [https://www.ebi.ac.uk/pdbsum/2k0n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2k0n ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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>
| + | [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> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| Line 32: |
Line 32: |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 18824]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Arthanari, H]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Frueh, D P]] | + | [[Category: Arthanari H]] |
| - | [[Category: Naar, A M]] | + | [[Category: Frueh DP]] |
| - | [[Category: Wagner, G K]] | + | [[Category: Naar AM]] |
| - | [[Category: Activator]] | + | [[Category: Wagner GK]] |
| - | [[Category: Nucleus]]
| + | |
| - | [[Category: Phosphoprotein]]
| + | |
| - | [[Category: Protein]]
| + | |
| - | [[Category: Transcription]]
| + | |
| - | [[Category: Transcription regulation]]
| + | |
| 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]
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
Multidrug resistance (MDR) is a serious complication during treatment of opportunistic fungal infections that frequently afflict immunocompromised individuals, such as transplant recipients and cancer patients undergoing cytotoxic chemotherapy. Improved knowledge of the molecular pathways controlling MDR in pathogenic fungi should facilitate the development of novel therapies to combat these intransigent infections. MDR is often caused by upregulation of drug efflux pumps by members of the fungal zinc-cluster transcription-factor family (for example Pdr1p orthologues). However, the molecular mechanisms are poorly understood. Here we show that Pdr1p family members in Saccharomyces cerevisiae and the human pathogen Candida glabrata directly bind to structurally diverse drugs and xenobiotics, resulting in stimulated expression of drug efflux pumps and induction of MDR. Notably, this is mechanistically similar to regulation of MDR in vertebrates by the PXR nuclear receptor, revealing an unexpected functional analogy of fungal and metazoan regulators of MDR. We have also uncovered a critical and specific role of the Gal11p/MED15 subunit of the Mediator co-activator and its activator-targeted KIX domain in antifungal/xenobiotic-dependent regulation of MDR. This detailed mechanistic understanding of a fungal nuclear receptor-like gene regulatory pathway provides novel therapeutic targets for the treatment of multidrug-resistant fungal infections.
A nuclear receptor-like pathway regulating multidrug resistance in fungi.,Thakur JK, Arthanari H, Yang F, Pan SJ, Fan X, Breger J, Frueh DP, Gulshan K, Li DK, Mylonakis E, Struhl K, Moye-Rowley WS, Cormack BP, Wagner G, Naar AM Nature. 2008 Apr 3;452(7187):604-9. PMID:18385733[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
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
- ↑ Thakur JK, Arthanari H, Yang F, Pan SJ, Fan X, Breger J, Frueh DP, Gulshan K, Li DK, Mylonakis E, Struhl K, Moye-Rowley WS, Cormack BP, Wagner G, Naar AM. A nuclear receptor-like pathway regulating multidrug resistance in fungi. Nature. 2008 Apr 3;452(7187):604-9. PMID:18385733 doi:10.1038/nature06836
|
