7n4v: Difference between revisions
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==Structure of cholesterol-bound human NPC1L1== | ==Structure of cholesterol-bound human NPC1L1== | ||
<StructureSection load='7n4v' size='340' side='right'caption='[[7n4v]]' scene=''> | <StructureSection load='7n4v' size='340' side='right'caption='[[7n4v]], [[Resolution|resolution]] 3.58Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N4V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N4V FirstGlance]. <br> | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N4V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N4V FirstGlance]. <br> | ||
</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=7n4v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n4v OCA], [https://pdbe.org/7n4v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n4v RCSB], [https://www.ebi.ac.uk/pdbsum/7n4v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n4v ProSAT]</span></td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.58Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</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=7n4v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n4v OCA], [https://pdbe.org/7n4v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n4v RCSB], [https://www.ebi.ac.uk/pdbsum/7n4v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n4v ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Polytopic Niemann-Pick C1-like 1 (NPC1L1) plays a major role in intestinal absorption of biliary cholesterol, vitamin E (VE), and vitamin K (VK). The drug ezetimibe inhibits NPC1L1-mediated absorption of cholesterol, lowering of circulating levels of low-density lipoprotein cholesterol. Here, we report cryo-electron microscopy structures of human NPC1L1 (hNPC1L1) bound to either cholesterol or a lipid resembling VE. These findings, together with functional assays, reveal that the same intramolecular channel in hNPC1L1 mediates transport of VE and cholesterol. hNPC1L1 exists primarily as a homodimer; dimerization is mediated by aromatic residues within a region of transmembrane helix 2 that exhibits a horizonal orientation in the membrane. Mutation of tryptophan-347 lies in this region disrupts dimerization and the resultant monomeric NPC1L1 exhibits reduced efficiency of cholesterol uptake. These findings identify the oligomeric state of hNPC1L1 as a target for therapies that inhibit uptake of dietary cholesterol and reduce the incidence of cardiovascular disease. | |||
Structures of dimeric human NPC1L1 provide insight into mechanisms for cholesterol absorption.,Long T, Liu Y, Qin Y, DeBose-Boyd RA, Li X Sci Adv. 2021 Aug 18;7(34). pii: 7/34/eabh3997. doi: 10.1126/sciadv.abh3997., Print 2021 Aug. PMID:34407950<ref>PMID:34407950</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7n4v" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 11:36, 30 October 2024
Structure of cholesterol-bound human NPC1L1
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