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| | ==Structural basis for aryl hydrocarbon receptor mediated gene activation== | | ==Structural basis for aryl hydrocarbon receptor mediated gene activation== |
| - | <StructureSection load='5nj8' size='340' side='right' caption='[[5nj8]], [[Resolution|resolution]] 3.30Å' scene=''> | + | <StructureSection load='5nj8' size='340' side='right'caption='[[5nj8]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5nj8]] is a 8 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NJ8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NJ8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5nj8]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NJ8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NJ8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ER3:ERBIUM+(III)+ION'>ER3</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.3Å</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=5nj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nj8 OCA], [http://pdbe.org/5nj8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nj8 RCSB], [http://www.ebi.ac.uk/pdbsum/5nj8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nj8 ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=ER3:ERBIUM+(III)+ION'>ER3</scene></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=5nj8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nj8 OCA], [https://pdbe.org/5nj8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nj8 RCSB], [https://www.ebi.ac.uk/pdbsum/5nj8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nj8 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AHR_HUMAN AHR_HUMAN]] Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.<ref>PMID:10395741</ref> <ref>PMID:7961644</ref> [[http://www.uniprot.org/uniprot/ARNT_HUMAN ARNT_HUMAN]] Required for activity of the Ah (dioxin) receptor. This protein is required for the ligand-binding subunit to translocate from the cytosol to the nucleus after ligand binding. The complex then initiates transcription of genes involved in the activation of PAH procarcinogens. The heterodimer with HIF1A or EPAS1/HIF2A functions as a transcriptional regulator of the adaptive response to hypoxia. | + | [https://www.uniprot.org/uniprot/AHR_HUMAN AHR_HUMAN] Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.<ref>PMID:10395741</ref> <ref>PMID:7961644</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 5nj8" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 5nj8" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[3D structures of hypoxia-inducible factor|3D structures of hypoxia-inducible factor]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Daumke, O]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Schulte, K W]] | + | [[Category: Large Structures]] |
| - | [[Category: Basic helix loop helix pas domain transcription factor]] | + | [[Category: Mus musculus]] |
| - | [[Category: Transcription]] | + | [[Category: Daumke O]] |
| | + | [[Category: Schulte KW]] |
| Structural highlights
Function
AHR_HUMAN Ligand-activated transcriptional activator. Binds to the XRE promoter region of genes it activates. Activates the expression of multiple phase I and II xenobiotic chemical metabolizing enzyme genes (such as the CYP1A1 gene). Mediates biochemical and toxic effects of halogenated aromatic hydrocarbons. Involved in cell-cycle regulation. Likely to play an important role in the development and maturation of many tissues. Regulates the circadian clock by inhibiting the basal and circadian expression of the core circadian component PER1. Inhibits PER1 by repressing the CLOCK-ARNTL/BMAL1 heterodimer mediated transcriptional activation of PER1.[1] [2]
Publication Abstract from PubMed
The aryl hydrocarbon receptor (AHR) and the AHR nuclear translocator (ARNT) constitute a heterodimeric basic helix-loop-helix-Per-ARNT-Sim (bHLH-PAS) domain containing transcription factor with central functions in development and cellular homeostasis. AHR is activated by xenobiotics, notably dioxin, as well as by exogenous and endogenous metabolites. Modulation of AHR activity holds promise for the treatment of diseases featuring altered cellular homeostasis, such as cancer or autoimmune disorders. Here, we present the crystal structure of a heterodimeric AHR:ARNT complex containing the PAS A and bHLH domain bound to its target DNA. The structure provides insights into the DNA binding mode of AHR and elucidates how stable dimerization of AHR:ARNT is achieved through sophisticated domain interplay via three specific interfaces. Using mutational analyses, we prove the relevance of the observed interfaces for AHR-mediated gene activation. Thus, our work establishes the structural basis of AHR assembly and DNA interaction and provides a template for targeted drug design.
Structural Basis for Aryl Hydrocarbon Receptor-Mediated Gene Activation.,Schulte KW, Green E, Wilz A, Platten M, Daumke O Structure. 2017 Jul 5;25(7):1025-1033.e3. doi: 10.1016/j.str.2017.05.008. Epub, 2017 Jun 9. PMID:28602820[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Nguyen TA, Hoivik D, Lee JE, Safe S. Interactions of nuclear receptor coactivator/corepressor proteins with the aryl hydrocarbon receptor complex. Arch Biochem Biophys. 1999 Jul 15;367(2):250-7. PMID:10395741 doi:http://dx.doi.org/10.1006/abbi.1999.1282
- ↑ Ema M, Ohe N, Suzuki M, Mimura J, Sogawa K, Ikawa S, Fujii-Kuriyama Y. Dioxin binding activities of polymorphic forms of mouse and human arylhydrocarbon receptors. J Biol Chem. 1994 Nov 4;269(44):27337-43. PMID:7961644
- ↑ Schulte KW, Green E, Wilz A, Platten M, Daumke O. Structural Basis for Aryl Hydrocarbon Receptor-Mediated Gene Activation. Structure. 2017 Jul 5;25(7):1025-1033.e3. doi: 10.1016/j.str.2017.05.008. Epub, 2017 Jun 9. PMID:28602820 doi:http://dx.doi.org/10.1016/j.str.2017.05.008
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