View source for 7dfz


==Cryo_EM structure of delta N-NPC1L1-EZE==
<StructureSection load='7dfz' size='340' side='right'caption='[[7dfz]], [[Resolution|resolution]] 3.58&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DFZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DFZ 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]] 3.58&#8491;</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=H56:(3~{R},4~{S})-1-(4-fluorophenyl)-3-[(3~{S})-3-(4-fluorophenyl)-3-oxidanyl-propyl]-4-(4-hydroxyphenyl)azetidin-2-one'>H56</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'>[https://proteopedia.org/fgij/fg.htm?mol=7dfz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dfz OCA], [https://pdbe.org/7dfz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dfz RCSB], [https://www.ebi.ac.uk/pdbsum/7dfz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dfz ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Niemann-Pick C1-like 1 (NPC1L1) protein plays a central role in the intestinal cholesterol absorption and is the target of a drug, ezetimibe, which inhibits NPC1L1 to reduce cholesterol absorption. Here, we present cryo-electron microscopy structures of human NPC1L1 in apo state, cholesterol-enriched state, and ezetimibe-bound state to reveal molecular details of NPC1L1-mediated cholesterol uptake and ezetimibe inhibition. Comparison of these structures reveals that the sterol-sensing domain (SSD) could respond to the cholesterol level alteration by binding different number of cholesterol molecules. Upon increasing cholesterol level, SSD binds more cholesterol molecules, which, in turn, triggers the formation of a stable structural cluster in SSD, while binding of ezetimibe causes the deformation of the SSD and destroys the structural cluster, leading to the inhibition of NPC1L1 function. These results provide insights into mechanisms of NPC1L1 function and ezetimibe action and are of great significance for the development of new cholesterol absorption inhibitors.

Structural insights into the mechanism of human NPC1L1-mediated cholesterol uptake.,Hu M, Yang F, Huang Y, You X, Liu D, Sun S, Sui SF Sci Adv. 2021 Jul 16;7(29). pii: 7/29/eabg3188. doi: 10.1126/sciadv.abg3188., Print 2021 Jul. PMID:34272236<ref>PMID:34272236</ref>

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