5i31 - Revision history

OCA: Redirecting to 5u73

OCA — Wed, 11 Oct 2017 06:42:10 GMT

Redirecting to 5u73

←Older revision		Revision as of 06:42, 11 October 2017
Line 1:		Line 1:
-		+	#REDIRECT [[5u73]] This PDB entry is obsolete and replaced by 5u73
-	~~==Crystal structure of human Niemann-Pick C1 protein==~~	+
-	~~<StructureSection load='5i31' size='340' side='right' caption='~~[[~~5i31~~]]~~, [[Resolution\|resolution]] 3.35Å' scene=''>~~	+
-	~~== Structural highlights ==~~	+
-	<table><tr><td colspan='2'>[[5i31]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I31 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I31 FirstGlance]. <br>	+
-	</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=5i31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i31 OCA], [http://pdbe.org/5i31 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i31 RCSB], [http://www.ebi.ac.uk/pdbsum/5i31 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i31 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 protein (NPC1) is a late-endosomal membrane protein involved in trafficking of LDL-derived cholesterol, Niemann-Pick disease type C, and Ebola virus infection. NPC1 contains 13 transmembrane segments (TMs), five of which are thought to represent a "sterol-sensing domain" (SSD). Although present also in other key regulatory proteins of cholesterol biosynthesis, uptake, and signaling, the structure and mechanism of action of the SSD are unknown. Here we report a crystal structure of a large fragment of human NPC1 at 3.6 A resolution, which reveals internal twofold pseudosymmetry along TM 2-13 and two structurally homologous domains that protrude 60 A into the endosomal lumen. Strikingly, NPC1's SSD forms a cavity that is accessible from both the luminal bilayer leaflet and the endosomal lumen; computational modeling suggests that this cavity is large enough to accommodate one cholesterol molecule. We propose a model for NPC1 function in cholesterol sensing and transport.	+
-		+
-	~~Structure of human Niemann-Pick C1 protein.,Li X, Wang J, Coutavas E, Shi H, Hao Q, Blobel G Proc Natl Acad Sci U S A. 2016 Jun 15. pii: 201607795. PMID:27307437<ref>PMID:27307437</ref>~~	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 5i31" style="background-color:#fffaf0;"></div>~~	+
-	~~== References ==~~	+
-	~~<references/>~~	+
-	~~__TOC__~~	+
-	~~</StructureSection>~~	+
-	~~[[Category: Blobel, G]]~~	+
-	~~[[Category: Li, X]]~~	+
-	~~[[Category: Wang, J]]~~	+
-	~~[[Category: Membrane protein]]~~	+

OCA at 10:24, 13 July 2016

OCA — Wed, 13 Jul 2016 10:24:24 GMT

←Older revision		Revision as of 10:24, 13 July 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5i31 is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of human Niemann-Pick C1 protein==
		+	<StructureSection load='5i31' size='340' side='right' caption='[[5i31]], [[Resolution\|resolution]] 3.35Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5i31]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I31 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I31 FirstGlance]. <br>
		+	</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=5i31 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i31 OCA], [http://pdbe.org/5i31 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i31 RCSB], [http://www.ebi.ac.uk/pdbsum/5i31 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i31 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 protein (NPC1) is a late-endosomal membrane protein involved in trafficking of LDL-derived cholesterol, Niemann-Pick disease type C, and Ebola virus infection. NPC1 contains 13 transmembrane segments (TMs), five of which are thought to represent a "sterol-sensing domain" (SSD). Although present also in other key regulatory proteins of cholesterol biosynthesis, uptake, and signaling, the structure and mechanism of action of the SSD are unknown. Here we report a crystal structure of a large fragment of human NPC1 at 3.6 A resolution, which reveals internal twofold pseudosymmetry along TM 2-13 and two structurally homologous domains that protrude 60 A into the endosomal lumen. Strikingly, NPC1's SSD forms a cavity that is accessible from both the luminal bilayer leaflet and the endosomal lumen; computational modeling suggests that this cavity is large enough to accommodate one cholesterol molecule. We propose a model for NPC1 function in cholesterol sensing and transport.

-	~~Authors: Li~~, X., Wang, J.	+	Structure of human Niemann-Pick C1 protein.,Li X, Wang J, Coutavas E, Shi H, Hao Q, Blobel G Proc Natl Acad Sci U S A. 2016 Jun 15. pii: 201607795. PMID:27307437<ref>PMID:27307437</ref>

-	~~Description: Structure of~~ a ~~membrane protein~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~[[Category~~: ~~Unreleased Structures]]~~	+	</div>
-	[[Category: ~~Wang~~, J]]	+	<div class="pdbe-citations 5i31" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Blobel, G]]
	[[Category: Li, X]]		[[Category: Li, X]]
		+	[[Category: Wang, J]]
		+	[[Category: Membrane protein]]

OCA at 19:15, 23 June 2016

OCA — Thu, 23 Jun 2016 19:15:09 GMT

←Older revision		Revision as of 19:15, 23 June 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5i31 is ON HOLD	+	The entry 5i31 is ON HOLD until Paper Publication

	Authors: Li, X., Wang, J.		Authors: Li, X., Wang, J.

OCA at 11:42, 20 June 2016

OCA — Mon, 20 Jun 2016 11:42:41 GMT

←Older revision		Revision as of 11:42, 20 June 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5i31 is ON HOLD ~~until Paper Publication~~	+	The entry 5i31 is ON HOLD

	Authors: Li, X., Wang, J.		Authors: Li, X., Wang, J.

OCA at 01:48, 10 March 2016

OCA — Thu, 10 Mar 2016 01:48:35 GMT

←Older revision		Revision as of 01:48, 10 March 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5i31 is ON HOLD	+	The entry 5i31 is ON HOLD until Paper Publication

	Authors: Li, X., Wang, J.		Authors: Li, X., Wang, J.

OCA: Protected "5i31" [edit=sysop:move=sysop]

OCA — Sun, 21 Feb 2016 01:30:50 GMT

Protected "5i31" [edit=sysop:move=sysop]

←Older revision

Revision as of 01:30, 21 February 2016

OCA: New page: '''Unreleased structure''' The entry 5i31 is ON HOLD Authors: Li, X., Wang, J. Description: Structure of a membrane protein Category: Unreleased Structures Category: Wang, J [[...

OCA — Sun, 21 Feb 2016 01:30:49 GMT

New page: '''Unreleased structure''' The entry 5i31 is ON HOLD Authors: Li, X., Wang, J. Description: Structure of a membrane protein Category: Unreleased Structures Category: Wang, J [[...

New page

'''Unreleased structure'''

The entry 5i31 is ON HOLD

Authors: Li, X., Wang, J.

Description: Structure of a membrane protein
[[Category: Unreleased Structures]]
[[Category: Wang, J]]
[[Category: Li, X]]