7vpu
From Proteopedia
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7vpu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Lachancea_thermotolerans_CBS_6340 Lachancea thermotolerans CBS 6340]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VPU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VPU FirstGlance]. <br> | <table><tr><td colspan='2'>[[7vpu]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Lachancea_thermotolerans_CBS_6340 Lachancea thermotolerans CBS 6340]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VPU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VPU FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ERG:ERGOSTEROL'>ERG</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]] 2.59Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ERG:ERGOSTEROL'>ERG</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=7vpu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vpu OCA], [https://pdbe.org/7vpu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vpu RCSB], [https://www.ebi.ac.uk/pdbsum/7vpu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vpu 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=7vpu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vpu OCA], [https://pdbe.org/7vpu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vpu RCSB], [https://www.ebi.ac.uk/pdbsum/7vpu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vpu ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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Fungal transcription factor Upc2 senses ergosterol levels and regulates sterol biosynthesis and uptake. Constitutive activation of Upc2 causes azole resistance in Candida species. We determined the structure of ergosterol-bound Upc2, revealing the ligand specificity and transcriptional regulation. Ergosterol binding involves conformational changes of the ligand-binding domain, creating a shape-complementary hydrophobic pocket. The conserved helix alpha12 and glycine-rich loop are critical for sterol recognition by forming the pocket wall. The mutations of the glycine-rich loop inhibit ligand binding by steric clashes and constitutively activate Upc2. The translocation of Upc2 is regulated by Hsp90 chaperone in a sterol-dependent manner. Ergosterol-bound Upc2 associates with Hsp90 using the C-terminal tail, which retains the inactive Upc2 in the cytosol. Ergosterol dissociation induces a conformational change of the C-terminal tail, releasing Upc2 from Hsp90 for nuclear transport by importin alpha. The understanding of the regulatory mechanism provides an antifungal target for the treatment of azole-resistant Candida infections. | Fungal transcription factor Upc2 senses ergosterol levels and regulates sterol biosynthesis and uptake. Constitutive activation of Upc2 causes azole resistance in Candida species. We determined the structure of ergosterol-bound Upc2, revealing the ligand specificity and transcriptional regulation. Ergosterol binding involves conformational changes of the ligand-binding domain, creating a shape-complementary hydrophobic pocket. The conserved helix alpha12 and glycine-rich loop are critical for sterol recognition by forming the pocket wall. The mutations of the glycine-rich loop inhibit ligand binding by steric clashes and constitutively activate Upc2. The translocation of Upc2 is regulated by Hsp90 chaperone in a sterol-dependent manner. Ergosterol-bound Upc2 associates with Hsp90 using the C-terminal tail, which retains the inactive Upc2 in the cytosol. Ergosterol dissociation induces a conformational change of the C-terminal tail, releasing Upc2 from Hsp90 for nuclear transport by importin alpha. The understanding of the regulatory mechanism provides an antifungal target for the treatment of azole-resistant Candida infections. | ||
| - | Structural basis for activation of fungal sterol receptor Upc2 and azole resistance.,Tan L, Chen L, Yang H, Jin B, Kim G, Im YJ Nat Chem Biol. 2022 | + | Structural basis for activation of fungal sterol receptor Upc2 and azole resistance.,Tan L, Chen L, Yang H, Jin B, Kim G, Im YJ Nat Chem Biol. 2022 Nov;18(11):1253-1262. doi: 10.1038/s41589-022-01117-0. Epub , 2022 Oct 13. PMID:36229681<ref>PMID:36229681</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
Current revision
Crystal structure of the ligand-binding domain of L. thermotolerans Upc2 in complex with ergosterol
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