5u74 - Revision history

OCA at 13:22, 4 October 2023

OCA — Wed, 04 Oct 2023 13:22:08 GMT

←Older revision		Revision as of 13:22, 4 October 2023
Line 3:		Line 3:
	<StructureSection load='5u74' size='340' side='right'caption='[[5u74]], [[Resolution\|resolution]] 3.33Å' scene=''>		<StructureSection load='5u74' size='340' side='right'caption='[[5u74]], [[Resolution\|resolution]] 3.33Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5u74]] 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=5U74 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5U74 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5u74]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U74 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U74 FirstGlance]. <br>
-	</td></tr><tr id='~~ligand~~'><td class="sblockLbl"><b>[[~~Ligand~~\|~~Ligands~~:]]</b></td><td class="sblockDat" id="~~ligandDat~~">~~<scene name='pdbligand=MES:2~~-~~(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>~~, ~~<scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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]] 3.335Å</td></tr>
-	<tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat">~~[[5u73\|5u73]]~~<~~/td~~></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=5u74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u74 OCA], [https://pdbe.org/5u74 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u74 RCSB], [https://www.ebi.ac.uk/pdbsum/5u74 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u74 ProSAT]</span></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=5u74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u74 OCA], [~~http~~://pdbe.org/5u74 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5u74 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5u74 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5u74 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>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 26:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Li, X]]	+	[[Category: Li X]]
-	~~[[Category: Membrane protein]]~~	+
-	~~[[Category: Npc1~~]]	+

OCA at 12:28, 23 September 2020

OCA — Wed, 23 Sep 2020 12:28:38 GMT

←Older revision		Revision as of 12:28, 23 September 2020
Line 1:		Line 1:

	==Structure of human Niemann-Pick C1 protein==		==Structure of human Niemann-Pick C1 protein==
-	<StructureSection load='5u74' size='340' side='right' caption='[[5u74]], [[Resolution\|resolution]] 3.33Å' scene=''>	+	<StructureSection load='5u74' size='340' side='right'caption='[[5u74]], [[Resolution\|resolution]] 3.33Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5u74]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U74 OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5U74 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5u74]] 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=5U74 OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5U74 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"~~><scene name~~=~~'pdbligand=MAN:ALPHA-D-MANNOSE'~~>~~MAN</scene>,~~ <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5u73\|5u73]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5u73\|5u73]]</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=5u74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u74 OCA], [http://pdbe.org/5u74 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u74 RCSB], [http://www.ebi.ac.uk/pdbsum/5u74 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u74 ProSAT]</span></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://proteopedia.org/fgij/fg.htm?mol=5u74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u74 OCA], [http://pdbe.org/5u74 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u74 RCSB], [http://www.ebi.ac.uk/pdbsum/5u74 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u74 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 25:		Line 26:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Li, X]]		[[Category: Li, X]]
	[[Category: Membrane protein]]		[[Category: Membrane protein]]
	[[Category: Npc1]]		[[Category: Npc1]]

OCA at 06:57, 11 October 2017

OCA — Wed, 11 Oct 2017 06:57:33 GMT

←Older revision		Revision as of 06:57, 11 October 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5u74 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Structure of human Niemann-Pick C1 protein==
		+	<StructureSection load='5u74' size='340' side='right' caption='[[5u74]], [[Resolution\|resolution]] 3.33Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5u74]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U74 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5U74 FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</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">[[5u73\|5u73]]</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=5u74 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u74 OCA], [http://pdbe.org/5u74 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u74 RCSB], [http://www.ebi.ac.uk/pdbsum/5u74 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u74 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 ==
		+	Niemann-Pick C1 (NPC1) and NPC2 proteins are indispensable for the export of LDL-derived cholesterol from late endosomes. Mutations in these proteins result in Niemann-Pick type C disease, a lysosomal storage disease. Despite recent reports of the NPC1 structure depicting its overall architecture, the function of its C-terminal luminal domain (CTD) remains poorly understood even though 45% of NPC disease-causing mutations are in this domain. Here, we report a crystal structure at 3.3 A resolution of NPC1* (residues 314-1,278), which-in contrast to previous lower resolution structures-features the entire CTD well resolved. Notably, all eight cysteines of the CTD form four disulfide bonds, one of which (C909-C914) enforces a specific loop that in turn mediates an interaction with a loop of the N-terminal domain (NTD). Importantly, this loop and its interaction with the NTD were not observed in any previous structures due to the lower resolution. Our mutagenesis experiments highlight the physiological relevance of the CTD-NTD interaction, which might function to keep the NTD in the proper orientation for receiving cholesterol from NPC2. Additionally, this structure allows us to more precisely map all of the disease-causing mutations, allowing future molecular insights into the pathogenesis of NPC disease.

-	~~Authors: Li~~, X.	+	3.3 A structure of Niemann-Pick C1 protein reveals insights into the function of the C-terminal luminal domain in cholesterol transport.,Li X, Lu F, Trinh MN, Schmiege P, Seemann J, Wang J, Blobel G Proc Natl Acad Sci U S A. 2017 Aug 22;114(34):9116-9121. doi:, 10.1073/pnas.1711716114. Epub 2017 Aug 7. PMID:28784760<ref>PMID:28784760</ref>

-	~~Description: cdc2~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
		+	<div class="pdbe-citations 5u74" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
	[[Category: Li, X]]		[[Category: Li, X]]
		+	[[Category: Membrane protein]]
		+	[[Category: Npc1]]

OCA at 16:20, 1 February 2017

OCA — Wed, 01 Feb 2017 16:20:48 GMT

←Older revision		Revision as of 16:20, 1 February 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5u74 is ON HOLD	+	The entry 5u74 is ON HOLD until Paper Publication

	Authors: Li, X.		Authors: Li, X.

OCA at 15:08, 2 January 2017

OCA — Mon, 02 Jan 2017 15:08:35 GMT

←Older revision		Revision as of 15:08, 2 January 2017
Line 3:		Line 3:
	The entry 5u74 is ON HOLD		The entry 5u74 is ON HOLD

-	Authors: Li, X	+	Authors: Li, X.

	Description: cdc2		Description: cdc2
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
	[[Category: Li, X]]		[[Category: Li, X]]

OCA: Protected "5u74" [edit=sysop:move=sysop]

OCA — Thu, 22 Dec 2016 20:29:07 GMT

Protected "5u74" [edit=sysop:move=sysop]

←Older revision

Revision as of 20:29, 22 December 2016

OCA: New page: '''Unreleased structure''' The entry 5u74 is ON HOLD Authors: Li, X Description: cdc2 Category: Unreleased Structures Category: Li, X

OCA — Thu, 22 Dec 2016 20:29:06 GMT

New page: '''Unreleased structure''' The entry 5u74 is ON HOLD Authors: Li, X Description: cdc2 Category: Unreleased Structures Category: Li, X

New page

'''Unreleased structure'''

The entry 5u74 is ON HOLD

Authors: Li, X

Description: cdc2
[[Category: Unreleased Structures]]
[[Category: Li, X]]