3gkj - Revision history

OCA at 20:07, 20 October 2021

OCA — Wed, 20 Oct 2021 20:07:49 GMT

←Older revision		Revision as of 20:07, 20 October 2021
Line 1:		Line 1:

	==NPC1D(NTD):25hydroxycholesterol==		==NPC1D(NTD):25hydroxycholesterol==
-	<StructureSection load='3gkj' size='340' side='right' caption='[[3gkj]], [[Resolution\|resolution]] 1.60Å' scene=''>	+	<StructureSection load='3gkj' size='340' side='right'caption='[[3gkj]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3gkj]] 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=3GKJ OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3GKJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3gkj]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GKJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3GKJ FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HC3:25-HYDROXYCHOLESTEROL'>HC3</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HC3:25-HYDROXYCHOLESTEROL'>HC3</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3gkh\|3gkh]], [[3gki\|3gki]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3gkh\|3gkh]], [[3gki\|3gki]]</div></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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">NPC1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3gkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gkj OCA], [~~http~~://pdbe.org/3gkj PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3gkj RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3gkj PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3gkj 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=3gkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gkj OCA], [https://pdbe.org/3gkj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3gkj RCSB], [https://www.ebi.ac.uk/pdbsum/3gkj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3gkj ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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>	+	[[https://www.uniprot.org/uniprot/NPC1_HUMAN NPC1_HUMAN]] Defects in NPC1 are the cause of Niemann-Pick disease type C1 (NPC1) [MIM:[https://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 ==		== 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>	+	[[https://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>
	== Evolutionary Conservation ==		== Evolutionary Conservation ==
	[[Image:Consurf_key_small.gif\|200px\|right]]		[[Image:Consurf_key_small.gif\|200px\|right]]
Line 37:		Line 37:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Kwon, H J]]		[[Category: Kwon, H J]]
	[[Category: Cholesterol]]		[[Category: Cholesterol]]

OCA at 05:20, 7 December 2018

OCA — Fri, 07 Dec 2018 05:20:41 GMT

←Older revision		Revision as of 05:20, 7 December 2018
Line 1:		Line 1:
		+
	==NPC1D(NTD):25hydroxycholesterol==		==NPC1D(NTD):25hydroxycholesterol==
	<StructureSection load='3gkj' size='340' side='right' caption='[[3gkj]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='3gkj' size='340' side='right' caption='[[3gkj]], [[Resolution\|resolution]] 1.60Å' scene=''>
Line 6:		Line 7:
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3gkh\|3gkh]], [[3gki\|3gki]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3gkh\|3gkh]], [[3gki\|3gki]]</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='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='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=3gkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gkj OCA], [http://pdbe.org/3gkj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gkj RCSB], [http://www.ebi.ac.uk/pdbsum/3gkj PDBsum]</span></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=3gkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gkj OCA], [http://pdbe.org/3gkj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gkj RCSB], [http://www.ebi.ac.uk/pdbsum/3gkj PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3gkj ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 16:		Line 17:
	Check<jmol>		Check<jmol>
	<jmolCheckbox>		<jmolCheckbox>
-	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gk/3gkj_consurf.spt"</scriptWhenChecked>	+	<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gk/3gkj_consurf.spt"</scriptWhenChecked>
	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>		<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>

OCA at 18:03, 8 February 2016

OCA — Mon, 08 Feb 2016 18:03:27 GMT

←Older revision		Revision as of 18:03, 8 February 2016
Line 2:		Line 2:
	<StructureSection load='3gkj' size='340' side='right' caption='[[3gkj]], [[Resolution\|resolution]] 1.60Å' scene=''>		<StructureSection load='3gkj' size='340' side='right' caption='[[3gkj]], [[Resolution\|resolution]] 1.60Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3gkj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Homo_sapiens Homo sapiens~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GKJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GKJ FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3gkj]] 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=3GKJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GKJ FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HC3:25-HYDROXYCHOLESTEROL'>HC3</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HC3:25-HYDROXYCHOLESTEROL'>HC3</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3gkh\|3gkh]], [[3gki\|3gki]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3gkh\|3gkh]], [[3gki\|3gki]]</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 ~~Homo sapiens~~])</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='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=3gkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gkj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3gkj RCSB], [http://www.ebi.ac.uk/pdbsum/3gkj PDBsum]</span></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=3gkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gkj OCA], [http://pdbe.org/3gkj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3gkj RCSB], [http://www.ebi.ac.uk/pdbsum/3gkj PDBsum]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 20:		Line 20:
	<text>to colour the structure by Evolutionary Conservation</text>		<text>to colour the structure by Evolutionary Conservation</text>
	</jmolCheckbox>		</jmolCheckbox>
-	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/~~chain_selection~~.php?pdb_ID=~~2ata~~ ConSurf].	+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3gkj ConSurf].
	<div style="clear:both"></div>		<div style="clear:both"></div>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
Line 30:		Line 30:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3gkj" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Homo sapiens~~]]	+	[[Category: Human]]
	[[Category: Kwon, H J]]		[[Category: Kwon, H J]]
	[[Category: Cholesterol]]		[[Category: Cholesterol]]

OCA at 15:55, 18 December 2014

OCA — Thu, 18 Dec 2014 15:55:37 GMT

←Older revision		Revision as of 15:55, 18 December 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3gkj~~\| ~~PDB~~=3gkj \| ~~SCENE~~= }}	+	==NPC1D(NTD):25hydroxycholesterol==
-	===~~NPC1D~~(~~NTD~~):~~25hydroxycholesterol~~===	+	<StructureSection load='3gkj' size='340' side='right' caption='[[3gkj]], [[Resolution\|resolution]] 1.60Å' scene=''>
-	~~{{ABSTRACT_PUBMED_19563754}}~~	+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3gkj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GKJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3GKJ FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HC3:25-HYDROXYCHOLESTEROL'>HC3</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3gkh\|3gkh]], [[3gki\|3gki]]</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 Homo sapiens])</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=3gkj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3gkj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3gkj RCSB], [http://www.ebi.ac.uk/pdbsum/3gkj PDBsum]</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>
		+	== Evolutionary Conservation ==
		+	[[Image:Consurf_key_small.gif\|200px\|right]]
		+	Check<jmol>
		+	<jmolCheckbox>
		+	<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gk/3gkj_consurf.spt"</scriptWhenChecked>
		+	<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
		+	<text>to colour the structure by Evolutionary Conservation</text>
		+	</jmolCheckbox>
		+	</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary\|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf].
		+	<div style="clear:both"></div>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	LDL delivers cholesterol to lysosomes by receptor-mediated endocytosis. Exit of cholesterol from lysosomes requires two proteins, membrane-bound Niemann-Pick C1 (NPC1) and soluble NPC2. NPC2 binds cholesterol with its isooctyl side chain buried and its 3beta-hydroxyl exposed. Here, we describe high-resolution structures of the N-terminal domain (NTD) of NPC1 and complexes with cholesterol and 25-hydroxycholesterol. NPC1(NTD) binds cholesterol in an orientation opposite to NPC2: 3beta-hydroxyl buried and isooctyl side chain exposed. Cholesterol transfer from NPC2 to NPC1(NTD) requires reorientation of a helical subdomain in NPC1(NTD), enlarging the opening for cholesterol entry. NPC1 with point mutations in this subdomain (distinct from the binding subdomain) cannot accept cholesterol from NPC2 and cannot restore cholesterol exit from lysosomes in NPC1-deficient cells. We propose a working model wherein after lysosomal hydrolysis of LDL-cholesteryl esters, cholesterol binds NPC2, which transfers it to NPC1(NTD), reversing its orientation and allowing insertion of its isooctyl side chain into the outer lysosomal membranes.

-	~~==Disease==~~	+	Structure of N-terminal domain of NPC1 reveals distinct subdomains for binding and transfer of cholesterol.,Kwon HJ, Abi-Mosleh L, Wang ML, Deisenhofer J, Goldstein JL, Brown MS, Infante RE Cell. 2009 Jun 26;137(7):1213-24. PMID:19563754<ref>PMID:19563754</ref>
-	~~[[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==~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[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>
-		+	== References ==
-	==~~About this Structure==~~	+	<references/>
-	[[3gkj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GKJ OCA].	+	__TOC__
-		+	</StructureSection>
-	~~==Reference~~==	+
-	~~<ref group="xtra">PMID:019563754</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
-	[[Category: Kwon, H J.]]	+	[[Category: Kwon, H J]]
	[[Category: Cholesterol]]		[[Category: Cholesterol]]
	[[Category: Cholesterol transfer]]		[[Category: Cholesterol transfer]]

OCA at 19:30, 24 March 2013

OCA — Sun, 24 Mar 2013 19:30:53 GMT

←Older revision		Revision as of 19:30, 24 March 2013
Line 1:		Line 1:
-	[[Image:3gkj.png\|left\|200px]]
-
	{{STRUCTURE_3gkj\| PDB=3gkj \| SCENE= }}		{{STRUCTURE_3gkj\| PDB=3gkj \| SCENE= }}
-
	===NPC1D(NTD):25hydroxycholesterol===		===NPC1D(NTD):25hydroxycholesterol===
		+	{{ABSTRACT_PUBMED_19563754}}

-	~~{{ABSTRACT_PUBMED_19563754}}~~	+	==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>

	==About this Structure==		==About this Structure==
Line 11:		Line 13:

	==Reference==		==Reference==
-	<ref group="xtra">PMID:019563754</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019563754</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Kwon, H J.]]		[[Category: Kwon, H J.]]

OCA: Protected "3gkj" [edit=sysop:move=sysop]

OCA — Wed, 27 Feb 2013 15:25:12 GMT

Protected "3gkj" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:25, 27 February 2013

OCA at 15:25, 27 February 2013

OCA — Wed, 27 Feb 2013 15:25:07 GMT

←Older revision		Revision as of 15:25, 27 February 2013
Line 1:		Line 1:
-	~~{{Seed}}~~	+	[[Image:3gkj.png\|left\|200px]]
-	[[Image:3gkj.~~jpg~~\|left\|200px]]	+

-	<!--
-	The line below this paragraph, containing "STRUCTURE_3gkj", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3gkj\| PDB=3gkj \| SCENE= }}		{{STRUCTURE_3gkj\| PDB=3gkj \| SCENE= }}

	===NPC1D(NTD):25hydroxycholesterol===		===NPC1D(NTD):25hydroxycholesterol===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_19563754}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 19563754 is the PubMed ID number.
-	-->
	{{ABSTRACT_PUBMED_19563754}}		{{ABSTRACT_PUBMED_19563754}}

	==About this Structure==		==About this Structure==
-	~~3GKJ~~ is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GKJ OCA].	+	[[3gkj]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GKJ OCA].

	==Reference==		==Reference==
-	<ref group="xtra">PMID:~~19563754~~</ref><references group="xtra"/>	+	<ref group="xtra">PMID:019563754</ref><references group="xtra"/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Kwon, H J.]]		[[Category: Kwon, H J.]]
Line 34:		Line 22:
	[[Category: Membrane]]		[[Category: Membrane]]
	[[Category: Oxysterol]]		[[Category: Oxysterol]]
-	[[Category: Polymorphism]]
	[[Category: Transmembrane]]		[[Category: Transmembrane]]
	[[Category: Transport protein]]		[[Category: Transport protein]]
-
-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 15 08:44:19 2009''

OCA at 05:44, 15 July 2009

OCA — Wed, 15 Jul 2009 05:44:21 GMT

←Older revision		Revision as of 05:44, 15 July 2009
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	{{Seed}}
		+	[[Image:3gkj.jpg\|left\|200px]]

-	The ~~entry 3gkj~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3gkj", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3gkj\| PDB=3gkj \| SCENE= }}

-	~~Authors~~: ~~Kwon, H.J.~~	+	===NPC1D(NTD):25hydroxycholesterol===

-	Description: NPC1D(NTD):25hydroxycholesterol

-	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed ~~Mar 25 12~~:16:45 2009''	+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_19563754}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 19563754 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_19563754}}
		+
		+	==About this Structure==
		+	3GKJ is a 1 chain structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3GKJ OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:19563754</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Kwon, H J.]]
		+	[[Category: Cholesterol]]
		+	[[Category: Cholesterol transfer]]
		+	[[Category: Disease mutation]]
		+	[[Category: Endosome]]
		+	[[Category: Glycoprotein]]
		+	[[Category: Lysosome]]
		+	[[Category: Membrane]]
		+	[[Category: Oxysterol]]
		+	[[Category: Polymorphism]]
		+	[[Category: Transmembrane]]
		+	[[Category: Transport protein]]
		+
		+	''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jul 15 08:44:19 2009''

OCA: New page: '''Unreleased structure''' The entry 3gkj is ON HOLD until Paper Publication Authors: Kwon, H.J. Description: NPC1D(NTD):25hydroxycholesterol ''Page seeded by [http://oca.weizmann.ac....

OCA — Wed, 25 Mar 2009 10:16:46 GMT

New page: '''Unreleased structure''' The entry 3gkj is ON HOLD until Paper Publication Authors: Kwon, H.J. Description: NPC1D(NTD):25hydroxycholesterol ''Page seeded by [http://oca.weizmann.ac....

New page

'''Unreleased structure'''

The entry 3gkj is ON HOLD until Paper Publication

Authors: Kwon, H.J.

Description: NPC1D(NTD):25hydroxycholesterol

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Mar 25 12:16:45 2009''