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| ==Structure and Dimerization Properties of the Aryl Hydrocarbon Receptor (AHR) PAS-A Domain== | | ==Structure and Dimerization Properties of the Aryl Hydrocarbon Receptor (AHR) PAS-A Domain== |
- | <StructureSection load='4m4x' size='340' side='right' caption='[[4m4x]], [[Resolution|resolution]] 2.55Å' scene=''> | + | <StructureSection load='4m4x' size='340' side='right'caption='[[4m4x]], [[Resolution|resolution]] 2.55Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[4m4x]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M4X OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4M4X FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4m4x]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4M4X OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M4X FirstGlance]. <br> |
- | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ahr ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</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]] 2.551Å</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=4m4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m4x OCA], [http://pdbe.org/4m4x PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4m4x RCSB], [http://www.ebi.ac.uk/pdbsum/4m4x PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4m4x 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=4m4x FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m4x OCA], [https://pdbe.org/4m4x PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m4x RCSB], [https://www.ebi.ac.uk/pdbsum/4m4x PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m4x ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/AHR_MOUSE AHR_MOUSE]] 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.<ref>PMID:1314586</ref> <ref>PMID:7961644</ref> <ref>PMID:7969080</ref> <ref>PMID:8806883</ref> <ref>PMID:9427285</ref> <ref>PMID:10973493</ref> <ref>PMID:10639156</ref> | + | [https://www.uniprot.org/uniprot/AHR_MOUSE AHR_MOUSE] 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.<ref>PMID:1314586</ref> <ref>PMID:7961644</ref> <ref>PMID:7969080</ref> <ref>PMID:8806883</ref> <ref>PMID:9427285</ref> <ref>PMID:10973493</ref> <ref>PMID:10639156</ref> |
- | <div style="background-color:#fffaf0;">
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- | == Publication Abstract from PubMed ==
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- | The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that binds to xenobiotics and responds by regulating the expression of gene programs required for detoxification and metabolism. AHR and its heterodimerization partner aryl hydrocarbon receptor nuclear translocator (ARNT) belong to the bHLH (basic helix-loop-helix)-PAS (PER-ARNT-SIM) family of transcription factors. Here we report the 2.55 A resolution crystal structure of the mouse AHR PAS-A domain, which represents the first AHR derived protein structure. The AHR PAS-A domain forms a helix-swapped homodimer in the crystal and also in solution. Through a detailed mutational analysis of all interface residues, we identified several hydrophobic residues that are important for the AHR dimerization and function. Our crystallographic visualization of the AHR PAS-A dimerization leads us to propose a mode of heterodimerization with ARNT that is supported by both biochemical and cell-based data. Our studies also highlight the residues of other mammalian bHLH-PAS proteins that are likely involved in their homo- or heterodimerization.
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- | Structure and Dimerization Properties of the Aryl Hydrocarbon Receptor (AHR) PAS-A Domain.,Wu D, Potluri N, Kim Y, Rastinejad F Mol Cell Biol. 2013 Sep 3. PMID:24001774<ref>PMID:24001774</ref>
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- | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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- | </div>
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- | <div class="pdbe-citations 4m4x" style="background-color:#fffaf0;"></div>
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| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
- | [[Category: Kim, Y]] | + | [[Category: Mus musculus]] |
- | [[Category: Potluri, N]] | + | [[Category: Kim Y]] |
- | [[Category: Rastinejad, F]] | + | [[Category: Potluri N]] |
- | [[Category: Wu, D]] | + | [[Category: Rastinejad F]] |
- | [[Category: Ahr]]
| + | [[Category: Wu D]] |
- | [[Category: Arnt]]
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- | [[Category: Dimer]]
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- | [[Category: Interface]]
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- | [[Category: Pas-a]]
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- | [[Category: Transcription]]
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- | [[Category: Transcription factor]]
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| Structural highlights
Function
AHR_MOUSE 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.[1] [2] [3] [4] [5] [6] [7]
References
- ↑ Ema M, Sogawa K, Watanabe N, Chujoh Y, Matsushita N, Gotoh O, Funae Y, Fujii-Kuriyama Y. cDNA cloning and structure of mouse putative Ah receptor. Biochem Biophys Res Commun. 1992 Apr 15;184(1):246-53. PMID:1314586
- ↑ 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
- ↑ Poland A, Palen D, Glover E. Analysis of the four alleles of the murine aryl hydrocarbon receptor. Mol Pharmacol. 1994 Nov;46(5):915-21. PMID:7969080
- ↑ Fernandez-Salguero PM, Hilbert DM, Rudikoff S, Ward JM, Gonzalez FJ. Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity. Toxicol Appl Pharmacol. 1996 Sep;140(1):173-9. PMID:8806883 doi:http://dx.doi.org/S0041-008X(96)90210-0
- ↑ Mimura J, Yamashita K, Nakamura K, Morita M, Takagi TN, Nakao K, Ema M, Sogawa K, Yasuda M, Katsuki M, Fujii-Kuriyama Y. Loss of teratogenic response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice lacking the Ah (dioxin) receptor. Genes Cells. 1997 Oct;2(10):645-54. PMID:9427285
- ↑ Lahvis GP, Lindell SL, Thomas RS, McCuskey RS, Murphy C, Glover E, Bentz M, Southard J, Bradfield CA. Portosystemic shunting and persistent fetal vascular structures in aryl hydrocarbon receptor-deficient mice. Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10442-7. PMID:10973493 doi:http://dx.doi.org/10.1073/pnas.190256997
- ↑ Shimizu Y, Nakatsuru Y, Ichinose M, Takahashi Y, Kume H, Mimura J, Fujii-Kuriyama Y, Ishikawa T. Benzo[a]pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor. Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):779-82. PMID:10639156
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