View source for 7vpr


==Crystal structure of the ligand-binding domain of C. glabrata Upc2 in complex with ergosterol==
<StructureSection load='7vpr' size='340' side='right'caption='[[7vpr]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7vpr]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Candida_glabrata_CBS_138 Candida glabrata CBS 138]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7VPR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7VPR FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.59&#8491;</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=7vpr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7vpr OCA], [https://pdbe.org/7vpr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7vpr RCSB], [https://www.ebi.ac.uk/pdbsum/7vpr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7vpr ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/Q6FX18_CANGA Q6FX18_CANGA] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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 Nov;18(11):1253-1262. doi: 10.1038/s41589-022-01117-0. Epub , 2022 Oct 13. PMID:36229681<ref>PMID:36229681</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7vpr" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Im YJ]]
[[Category: Tan L]]