View source for 8qec


==S. cerevisia Niemann-Pick type C protein NCR1 in GDN at pH 5.5==
<StructureSection load='8qec' size='340' side='right'caption='[[8qec]], [[Resolution|resolution]] 3.30&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8qec]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8QEC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QEC FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.3&#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>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Q7G:(2~{R},3~{S},4~{S},5~{R},6~{R})-2-(hydroxymethyl)-6-[(2~{R},3~{S},4~{R},5~{R},6~{S})-2-(hydroxymethyl)-6-[2-[[(2~{S},3~{R},4~{R},5~{S},6~{R})-6-(hydroxymethyl)-5-[(2~{R},3~{R},4~{S},5~{S},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-3,4-bis(oxidanyl)oxan-2-yl]oxymethyl]-4-[(1~{S},2~{S},4~{S},5~{R},6~{R},7~{S},8~{R},9~{S},12~{S},13~{R},16~{S})-5,7,9,13-tetramethylspiro[5-oxapentacyclo[10.8.0.0^{2,9}.0^{4,8}.0^{13,18}]icos-18-ene-6,2-oxane]-16-yl]oxy-butoxy]-4,5-bis(oxidanyl)oxan-3-yl]oxy-oxane-3,4,5-triol'>Q7G</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=8qec FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qec OCA], [https://pdbe.org/8qec PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qec RCSB], [https://www.ebi.ac.uk/pdbsum/8qec PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qec ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/NPC1_YEAST NPC1_YEAST] Involved in sphingolipid trafficking. May recycle sphingolipids between cellular membranous compartments.<ref>PMID:14970192</ref> <ref>PMID:16138904</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The membrane protein Niemann-Pick type C1 (NPC1, named NCR1 in yeast) is central to sterol homeostasis in eukaryotes. Saccharomyces cerevisiae NCR1 is localized to the vacuolar membrane, where it is suggested to carry sterols across the protective glycocalyx and deposit them into the vacuolar membrane. However, documentation of a vacuolar glycocalyx in fungi is lacking, and the mechanism for sterol translocation has remained unclear. Here, we provide evidence supporting the presence of a glycocalyx in isolated S. cerevisiae vacuoles and report four cryo-EM structures of NCR1 in two distinct conformations, named tense and relaxed. These two conformations illustrate the movement of sterols through a tunnel formed by the luminal domains, thus bypassing the barrier presented by the glycocalyx. Based on these structures and on comparison with other members of the Resistance-Nodulation-Division (RND) superfamily, we propose a transport model that links changes in the luminal domains with a cycle of protonation and deprotonation within the transmembrane region of the protein. Our model suggests that NPC proteins work by a generalized RND mechanism where the proton motive force drives conformational changes in the transmembrane domains that are allosterically coupled to luminal/extracellular domains to promote sterol transport.

Conformational changes in the Niemann-Pick type C1 protein NCR1 drive sterol translocation.,Frain KM, Dedic E, Nel L, Bohush A, Olesen E, Thaysen K, Wustner D, Stokes DL, Pedersen BP Proc Natl Acad Sci U S A. 2024 Apr 9;121(15):e2315575121. doi: , 10.1073/pnas.2315575121. Epub 2024 Apr 3. PMID:38568972<ref>PMID:38568972</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8qec" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Dedic E]]
[[Category: Frain KM]]
[[Category: Nel L]]
[[Category: Olesen E]]
[[Category: Panyella Pedersen B]]
[[Category: Stokes D]]