6w5t: Difference between revisions

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 <StructureSection load='6w5t' size='340' side='right'caption='[[6w5t]], [[Resolution|resolution]] 3.70&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6w5t]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W5T OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6W5T FirstGlance]. <br>
+<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6W5T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6W5T FirstGlance]. <br>
-</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=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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">Electron Microscopy, [[Resolution|Resolution]] 3.7&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">NPC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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://proteopedia.org/fgij/fg.htm?mol=6w5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w5t OCA], [http://pdbe.org/6w5t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6w5t RCSB], [http://www.ebi.ac.uk/pdbsum/6w5t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6w5t 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=6w5t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6w5t OCA], [https://pdbe.org/6w5t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6w5t RCSB], [https://www.ebi.ac.uk/pdbsum/6w5t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6w5t ProSAT]</span></td></tr>
 </table>
-== Disease ==
-[[http://www.uniprot.org/uniprot/NPC1_HUMAN NPC1_HUMAN]] Defects in NPC1 are the cause of Niemann-Pick disease type C1 (NPC1) [MIM:[http://omim.org/entry/257220 257220]]. A lysosomal storage disorder that affects the viscera and the central nervous system. It is due to defective intracellular processing and transport of low-density lipoprotein derived cholesterol. It causes accumulation of cholesterol in lysosomes, with delayed induction of cholesterol homeostatic reactions. Niemann-Pick disease type C1 has a highly variable clinical phenotype. Clinical features include variable hepatosplenomegaly and severe progressive neurological dysfunction such as ataxia, dystonia and dementia. The age of onset can vary from infancy to late adulthood. An allelic variant of Niemann-Pick disease type C1 is found in people with Nova Scotia ancestry. Patients with the Nova Scotian clinical variant are less severely affected.<ref>PMID:9211849</ref> <ref>PMID:11754101</ref> <ref>PMID:9634529</ref> <ref>PMID:10521290</ref> <ref>PMID:10521297</ref> <ref>PMID:10480349</ref> <ref>PMID:11182931</ref> <ref>PMID:11349231</ref> <ref>PMID:11333381</ref> <ref>PMID:11545687</ref> <ref>PMID:11479732</ref> <ref>PMID:12408188</ref> <ref>PMID:12401890</ref> <ref>PMID:12554680</ref> <ref>PMID:12955717</ref> <ref>PMID:16098014</ref> <ref>PMID:15774455</ref> <ref>PMID:16126423</ref> <ref>PMID:16802107</ref>
-== Function ==
-[[http://www.uniprot.org/uniprot/NPC1_HUMAN NPC1_HUMAN]] Intracellular cholesterol transporter which acts in concert with NPC2 and plays an important role in the egress of cholesterol from the endosomal/lysosomal compartment. Both NPC1 and NPC2 function as the cellular 'tag team duo' (TTD) to catalyze the mobilization of cholesterol within the multivesicular environment of the late endosome (LE) to effect egress through the limiting bilayer of the LE. NPC2 binds unesterified cholesterol that has been released from LDLs in the lumen of the late endosomes/lysosomes and transfers it to the cholesterol-binding pocket of the N-terminal domain of NPC1. Cholesterol binds to NPC1 with the hydroxyl group buried in the binding pocket and is exported from the limiting membrane of late endosomes/ lysosomes to the ER and plasma membrane by an unknown mechanism. Binds oxysterol with higher affinity than cholesterol. May play a role in vesicular trafficking in glia, a process that may be crucial for maintaining the structural and functional integrity of nerve terminals.<ref>PMID:18772377</ref>
-<div style="background-color:#fffaf0;">
-== Publication Abstract from PubMed ==
-Lysosomal cholesterol egress requires two proteins, NPC1 and NPC2, whose defects are responsible for Niemann-Pick disease type C (NPC). Here, we present systematic structural characterizations that reveal the molecular basis for low-pH-dependent cholesterol delivery from NPC2 to the transmembrane (TM) domain of NPC1. At pH 8.0, similar structures of NPC1 were obtained in nanodiscs and in detergent at resolutions of 3.6 A and 3.0 A, respectively. A tunnel connecting the N-terminal domain (NTD) and the transmembrane sterol-sensing domain (SSD) was unveiled. At pH 5.5, the NTD exhibits two conformations, suggesting the motion for cholesterol delivery to the tunnel. A putative cholesterol molecule is found at the membrane boundary of the tunnel, and TM2 moves toward formation of a surface pocket on the SSD. Finally, the structure of the NPC1-NPC2 complex at 4.0 A resolution was obtained at pH 5.5, elucidating the molecular basis for cholesterol handoff from NPC2 to NPC1(NTD).
-Structural Basis of Low-pH-Dependent Lysosomal Cholesterol Egress by NPC1 and NPC2.,Qian H, Wu X, Du X, Yao X, Zhao X, Lee J, Yang H, Yan N Cell. 2020 Jun 11. pii: S0092-8674(20)30615-2. doi: 10.1016/j.cell.2020.05.020. PMID:32544384<ref>PMID:32544384</ref>
-From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-</div>
-<div class="pdbe-citations 6w5t" style="background-color:#fffaf0;"></div>
-== References ==
-<references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
 [[Category: Large Structures]]
-[[Category: Qian, H W]]
+[[Category: Qian HW]]
-[[Category: Wu, X L]]
+[[Category: Wu XL]]
-[[Category: Yan, N]]
+[[Category: Yan N]]
-[[Category: Cholesterol lysosome]]
-[[Category: Transport protein]]