7zub
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7zub]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZUB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZUB FirstGlance]. <br> | <table><tr><td colspan='2'>[[7zub]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7ZUB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZUB FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=JY6:(3~{Z})-3-(3-oxidanylidene-1~{H}-indol-2-ylidene)-1~{H}-indol-2-one'>JY6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MOO:MOLYBDATE+ION'>MOO</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.85Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=JY6:(3~{Z})-3-(3-oxidanylidene-1~{H}-indol-2-ylidene)-1~{H}-indol-2-one'>JY6</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MOO:MOLYBDATE+ION'>MOO</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=7zub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zub OCA], [https://pdbe.org/7zub PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zub RCSB], [https://www.ebi.ac.uk/pdbsum/7zub PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zub 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=7zub FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zub OCA], [https://pdbe.org/7zub PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zub RCSB], [https://www.ebi.ac.uk/pdbsum/7zub PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zub ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | [https://www.uniprot.org/uniprot/ | + | [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;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates a broad spectrum of (patho)physiological processes in response to numerous substances including pollutants, natural products and metabolites. However, the scarcity of structural data precludes understanding of how AHR is activated by such diverse compounds. Our 2.85 A structure of the human indirubin-bound AHR complex with the chaperone Hsp90 and the co-chaperone XAP2, reported herein, reveals a closed conformation Hsp90 dimer with AHR threaded through its lumen and XAP2 serving as a brace. Importantly, we disclose the long-awaited structure of the AHR PAS-B domain revealing a unique organisation of the ligand-binding pocket and the structural determinants of ligand-binding specificity and promiscuity of the receptor. By providing structural details of the molecular initiating event leading to AHR activation, our study rationalises almost forty years of biochemical data and provides a framework for future mechanistic studies and structure-guided drug design. | ||
| + | |||
| + | Cryo-EM structure of the agonist-bound Hsp90-XAP2-AHR cytosolic complex.,Gruszczyk J, Grandvuillemin L, Lai-Kee-Him J, Paloni M, Savva CG, Germain P, Grimaldi M, Boulahtouf A, Kwong HS, Bous J, Ancelin A, Bechara C, Barducci A, Balaguer P, Bourguet W Nat Commun. 2022 Nov 16;13(1):7010. doi: 10.1038/s41467-022-34773-w. PMID:36385050<ref>PMID:36385050</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7zub" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Heat Shock Protein structures|Heat Shock Protein structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Cryo-EM structure of the indirubin-bound Hsp90-XAP2-AHR complex
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