View source for 7vpu


==Crystal structure of the ligand-binding domain of L. thermotolerans Upc2 in complex with ergosterol==
<StructureSection load='7vpu' size='340' side='right'caption='[[7vpu]], [[Resolution|resolution]] 2.59&Aring;' scene=''>
== 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>
</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=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>
== Function ==
[https://www.uniprot.org/uniprot/C5DKV6_LACTC C5DKV6_LACTC] 
<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 7vpu" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Lachancea thermotolerans CBS 6340]]
[[Category: Large Structures]]
[[Category: Im YJ]]
[[Category: Tan L]]