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| | <StructureSection load='6r4l' size='340' side='right'caption='[[6r4l]], [[Resolution|resolution]] 3.50Å' scene=''> | | <StructureSection load='6r4l' size='340' side='right'caption='[[6r4l]], [[Resolution|resolution]] 3.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6r4l]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R4L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6R4L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6r4l]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6R4L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6R4L FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=ERG:ERGOSTEROL'>ERG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 3.5Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NCR1, YPL006W ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=ERG:ERGOSTEROL'>ERG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6r4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r4l OCA], [http://pdbe.org/6r4l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6r4l RCSB], [http://www.ebi.ac.uk/pdbsum/6r4l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6r4l 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=6r4l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6r4l OCA], [https://pdbe.org/6r4l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6r4l RCSB], [https://www.ebi.ac.uk/pdbsum/6r4l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6r4l ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Baker's yeast]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Kidmose, R T]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
| - | [[Category: Pedersen, B P]] | + | [[Category: Kidmose RT]] |
| - | [[Category: Winkler, M B.L]] | + | [[Category: Pedersen BP]] |
| - | [[Category: Ergosterol]] | + | [[Category: Winkler MBL]] |
| - | [[Category: Lipid transport]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Vacuole]]
| + | |
| Structural highlights
Function
NPC1_YEAST Involved in sphingolipid trafficking. May recycle sphingolipids between cellular membranous compartments.[1] [2]
Publication Abstract from PubMed
Niemann-Pick type C (NPC) proteins are essential for sterol homeostasis, believed to drive sterol integration into the lysosomal membrane before redistribution to other cellular membranes. Here, using a combination of crystallography, cryo-electron microscopy, and biochemical and in vivo studies on the Saccharomyces cerevisiae NPC system (NCR1 and NPC2), we present a framework for sterol membrane integration. Sterols are transferred between hydrophobic pockets of vacuolar NPC2 and membrane-protein NCR1. NCR1 has its N-terminal domain (NTD) positioned to deliver a sterol to a tunnel connecting NTD to the luminal membrane leaflet 50 A away. A sterol is caught inside this tunnel during transport, and a proton-relay network of charged residues in the transmembrane region is linked to this tunnel supporting a proton-driven transport mechanism. We propose a model for sterol integration that clarifies the role of NPC proteins in this essential eukaryotic pathway and that rationalizes mutations in patients with Niemann-Pick disease type C.
Structural Insight into Eukaryotic Sterol Transport through Niemann-Pick Type C Proteins.,Winkler MBL, Kidmose RT, Szomek M, Thaysen K, Rawson S, Muench SP, Wustner D, Pedersen BP Cell. 2019 Oct 3;179(2):485-497.e18. doi: 10.1016/j.cell.2019.08.038. Epub 2019, Sep 19. PMID:31543266[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Malathi K, Higaki K, Tinkelenberg AH, Balderes DA, Almanzar-Paramio D, Wilcox LJ, Erdeniz N, Redican F, Padamsee M, Liu Y, Khan S, Alcantara F, Carstea ED, Morris JA, Sturley SL. Mutagenesis of the putative sterol-sensing domain of yeast Niemann Pick C-related protein reveals a primordial role in subcellular sphingolipid distribution. J Cell Biol. 2004 Feb 16;164(4):547-56. PMID:14970192 doi:http://dx.doi.org/10.1083/jcb.200310046
- ↑ Berger AC, Hanson PK, Wylie Nichols J, Corbett AH. A yeast model system for functional analysis of the Niemann-Pick type C protein 1 homolog, Ncr1p. Traffic. 2005 Oct;6(10):907-17. PMID:16138904 doi:http://dx.doi.org/TRA327
- ↑ Winkler MBL, Kidmose RT, Szomek M, Thaysen K, Rawson S, Muench SP, Wustner D, Pedersen BP. Structural Insight into Eukaryotic Sterol Transport through Niemann-Pick Type C Proteins. Cell. 2019 Oct 3;179(2):485-497.e18. doi: 10.1016/j.cell.2019.08.038. Epub 2019, Sep 19. PMID:31543266 doi:http://dx.doi.org/10.1016/j.cell.2019.08.038
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