6v7m - Revision history

OCA at 08:05, 11 October 2023

2023-10-11T08:05:19Z

←Older revision		Revision as of 08:05, 11 October 2023
Line 3:		Line 3:
	<StructureSection load='6v7m' size='340' side='right'caption='[[6v7m]], [[Resolution\|resolution]] 2.00Å' scene=''>		<StructureSection load='6v7m' size='340' side='right'caption='[[6v7m]], [[Resolution\|resolution]] 2.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6v7m]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V7M OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=6V7M FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6v7m]] is a 2 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=6V7M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V7M FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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]] 2Å</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=6v7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v7m OCA], [~~http~~://pdbe.org/6v7m PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=6v7m RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/6v7m PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=6v7m ProSAT]</span></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=6v7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v7m OCA], [https://pdbe.org/6v7m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v7m RCSB], [https://www.ebi.ac.uk/pdbsum/6v7m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v7m ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/APOE_HUMAN APOE_HUMAN]] Defects in APOE are a cause of hyperlipoproteinemia type 3 (HLPP3) [MIM:[~~http~~://omim.org/entry/107741 107741]]; also known as familial dysbetalipoproteinemia. Individuals with HLPP3 are clinically characterized by xanthomas, yellowish lipid deposits in the palmar crease, or less specific on tendons and on elbows. The disorder rarely manifests before the third decade in men. In women, it is usually expressed only after the menopause. The vast majority of the patients are homozygous for APOE2 alleles. More severe cases of HLPP3 have also been observed in individuals heterozygous for rare APOE variants. The influence of APOE on lipid levels is often suggested to have major implications for the risk of coronary artery disease (CAD). Individuals carrying the common APOE4 variant are at higher risk of CAD.<ref>PMID:8346443</ref> <ref>PMID:2556398</ref> <ref>PMID:1674745</ref> <ref>PMID:8287539</ref> <ref>PMID:22481068</ref> Genetic variations in APOE are associated with Alzheimer disease type 2 (AD2) [MIM:[~~http~~://omim.org/entry/104310 104310]]. It is a late-onset neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death. Note=The APOE4 allele is genetically associated with the common late onset familial and sporadic forms of Alzheimer disease. Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE4 alleles in 42 families with late onset AD. Thus APOE4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE4 was virtually sufficient to cause AD by age 80. The mechanism by which APOE*4 participates in pathogenesis is not known.<ref>PMID:8346443</ref> Defects in APOE are a cause of sea-blue histiocyte disease (SBHD) [MIM:[~~http~~://omim.org/entry/269600 269600]]; also known as sea-blue histiocytosis. This disorder is characterized by splenomegaly, mild thrombocytopenia and, in the bone marrow, numerous histiocytes containing cytoplasmic granules which stain bright blue with the usual hematologic stains. The syndrome is the consequence of an inherited metabolic defect analogous to Gaucher disease and other sphingolipidoses.<ref>PMID:8346443</ref> <ref>PMID:11095479</ref> <ref>PMID:16094309</ref> Defects in APOE are a cause of lipoprotein glomerulopathy (LPG) [MIM:[~~http~~://omim.org/entry/611771 611771]]. LPG is an uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries. It mainly affects people of Japanese and Chinese origin. The disorder has rarely been described in Caucasians.<ref>PMID:8346443</ref> <ref>PMID:9176854</ref> <ref>PMID:10432380</ref> <ref>PMID:18077821</ref> Defects in APOE are a cause of familial hypercholesterolemia (FH) [MIM:[~~http~~://omim.org/entry/143890 143890]]. FH is a condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:8346443</ref> <ref>PMID:22949395</ref>	+	[https://www.uniprot.org/uniprot/APOE_HUMAN APOE_HUMAN] Defects in APOE are a cause of hyperlipoproteinemia type 3 (HLPP3) [MIM:[https://omim.org/entry/107741 107741]; also known as familial dysbetalipoproteinemia. Individuals with HLPP3 are clinically characterized by xanthomas, yellowish lipid deposits in the palmar crease, or less specific on tendons and on elbows. The disorder rarely manifests before the third decade in men. In women, it is usually expressed only after the menopause. The vast majority of the patients are homozygous for APOE2 alleles. More severe cases of HLPP3 have also been observed in individuals heterozygous for rare APOE variants. The influence of APOE on lipid levels is often suggested to have major implications for the risk of coronary artery disease (CAD). Individuals carrying the common APOE4 variant are at higher risk of CAD.<ref>PMID:8346443</ref> <ref>PMID:2556398</ref> <ref>PMID:1674745</ref> <ref>PMID:8287539</ref> <ref>PMID:22481068</ref> Genetic variations in APOE are associated with Alzheimer disease type 2 (AD2) [MIM:[https://omim.org/entry/104310 104310]. It is a late-onset neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death. Note=The APOE4 allele is genetically associated with the common late onset familial and sporadic forms of Alzheimer disease. Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE4 alleles in 42 families with late onset AD. Thus APOE4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE4 was virtually sufficient to cause AD by age 80. The mechanism by which APOE*4 participates in pathogenesis is not known.<ref>PMID:8346443</ref> Defects in APOE are a cause of sea-blue histiocyte disease (SBHD) [MIM:[https://omim.org/entry/269600 269600]; also known as sea-blue histiocytosis. This disorder is characterized by splenomegaly, mild thrombocytopenia and, in the bone marrow, numerous histiocytes containing cytoplasmic granules which stain bright blue with the usual hematologic stains. The syndrome is the consequence of an inherited metabolic defect analogous to Gaucher disease and other sphingolipidoses.<ref>PMID:8346443</ref> <ref>PMID:11095479</ref> <ref>PMID:16094309</ref> Defects in APOE are a cause of lipoprotein glomerulopathy (LPG) [MIM:[https://omim.org/entry/611771 611771]. LPG is an uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries. It mainly affects people of Japanese and Chinese origin. The disorder has rarely been described in Caucasians.<ref>PMID:8346443</ref> <ref>PMID:9176854</ref> <ref>PMID:10432380</ref> <ref>PMID:18077821</ref> Defects in APOE are a cause of familial hypercholesterolemia (FH) [MIM:[https://omim.org/entry/143890 143890]. FH is a condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:8346443</ref> <ref>PMID:22949395</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/APOE_HUMAN APOE_HUMAN]] Mediates the binding, internalization, and catabolism of lipoprotein particles. It can serve as a ligand for the LDL (apo B/E) receptor and for the specific apo-E receptor (chylomicron remnant) of hepatic tissues.	+	[https://www.uniprot.org/uniprot/APOE_HUMAN APOE_HUMAN] Mediates the binding, internalization, and catabolism of lipoprotein particles. It can serve as a ligand for the LDL (apo B/E) receptor and for the specific apo-E receptor (chylomicron remnant) of hepatic tissues.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 24:		Line 25:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: McPherson, A]]	+	[[Category: McPherson A]]
-	~~[[Category: Alzheimer]]~~	+
-	~~[[Category: Disease]]~~	+
-	~~[[Category: Lipid]]~~	+
-	~~[[Category: Lipid transport]]~~	+
-	~~[[Category: Lipoprotein]]~~	+
-	~~[[Category: Proteolysis~~]]	+

OCA at 07:31, 11 March 2020

2020-03-11T07:31:00Z

←Older revision		Revision as of 07:31, 11 March 2020
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The entry ~~6v7m~~ is ~~ON HOLD~~	+	==Crystal structure of a proteolytically cleaved, amino terminal domain of apolipoprotein E3==
		+	<StructureSection load='6v7m' size='340' side='right'caption='[[6v7m]], [[Resolution\|resolution]] 2.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6v7m]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V7M OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6V7M FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></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=6v7m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v7m OCA], [http://pdbe.org/6v7m PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v7m RCSB], [http://www.ebi.ac.uk/pdbsum/6v7m PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v7m ProSAT]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/APOE_HUMAN APOE_HUMAN]] Defects in APOE are a cause of hyperlipoproteinemia type 3 (HLPP3) [MIM:[http://omim.org/entry/107741 107741]]; also known as familial dysbetalipoproteinemia. Individuals with HLPP3 are clinically characterized by xanthomas, yellowish lipid deposits in the palmar crease, or less specific on tendons and on elbows. The disorder rarely manifests before the third decade in men. In women, it is usually expressed only after the menopause. The vast majority of the patients are homozygous for APOE2 alleles. More severe cases of HLPP3 have also been observed in individuals heterozygous for rare APOE variants. The influence of APOE on lipid levels is often suggested to have major implications for the risk of coronary artery disease (CAD). Individuals carrying the common APOE4 variant are at higher risk of CAD.<ref>PMID:8346443</ref> <ref>PMID:2556398</ref> <ref>PMID:1674745</ref> <ref>PMID:8287539</ref> <ref>PMID:22481068</ref> Genetic variations in APOE are associated with Alzheimer disease type 2 (AD2) [MIM:[http://omim.org/entry/104310 104310]]. It is a late-onset neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death. Note=The APOE4 allele is genetically associated with the common late onset familial and sporadic forms of Alzheimer disease. Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE4 alleles in 42 families with late onset AD. Thus APOE4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE4 was virtually sufficient to cause AD by age 80. The mechanism by which APOE*4 participates in pathogenesis is not known.<ref>PMID:8346443</ref> Defects in APOE are a cause of sea-blue histiocyte disease (SBHD) [MIM:[http://omim.org/entry/269600 269600]]; also known as sea-blue histiocytosis. This disorder is characterized by splenomegaly, mild thrombocytopenia and, in the bone marrow, numerous histiocytes containing cytoplasmic granules which stain bright blue with the usual hematologic stains. The syndrome is the consequence of an inherited metabolic defect analogous to Gaucher disease and other sphingolipidoses.<ref>PMID:8346443</ref> <ref>PMID:11095479</ref> <ref>PMID:16094309</ref> Defects in APOE are a cause of lipoprotein glomerulopathy (LPG) [MIM:[http://omim.org/entry/611771 611771]]. LPG is an uncommon kidney disease characterized by proteinuria, progressive kidney failure, and distinctive lipoprotein thrombi in glomerular capillaries. It mainly affects people of Japanese and Chinese origin. The disorder has rarely been described in Caucasians.<ref>PMID:8346443</ref> <ref>PMID:9176854</ref> <ref>PMID:10432380</ref> <ref>PMID:18077821</ref> Defects in APOE are a cause of familial hypercholesterolemia (FH) [MIM:[http://omim.org/entry/143890 143890]]. FH is a condition characterized by elevated circulating cholesterol contained in either low-density lipoproteins alone or also in very-low-density lipoproteins.<ref>PMID:8346443</ref> <ref>PMID:22949395</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/APOE_HUMAN APOE_HUMAN]] Mediates the binding, internalization, and catabolism of lipoprotein particles. It can serve as a ligand for the LDL (apo B/E) receptor and for the specific apo-E receptor (chylomicron remnant) of hepatic tissues.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	A sample of Apolipoprotein E3 used in the original structure determination by X-ray crystallography (PDB code 1NFN) was crystallized under different conditions and its structure determined by molecular replacement at 298 degrees K. The original model (1NFN) began at amino acid 23 and ended at amino acid 164, but the amino acid segment 81 through 91 (a loop between helices) was not visible in the electron density and presumed disordered. The model reported here is essentially identical to 1NFN, but now includes amino acids 18 through 22 at the amino terminus, 165 at the carboxy terminus and includes as well the segment 83 through 91. Leu 82 is not visible, but the separation between Gln 81 and Thr 83 is more than 10 A, thereby indicating a proteolytic cleavage occurred between those two residues.

-	~~Authors: McPherson~~, A.	+	Crystal structure of a proteolytically cleaved, amino terminal domain of apolipoprotein E3.,McPherson A Biochem Biophys Res Commun. 2020 Feb 17. pii: S0006-291X(20)30194-7. doi:, 10.1016/j.bbrc.2020.01.117. PMID:32081433<ref>PMID:32081433</ref>

-	~~Description: Crystal structure of a proteolytically cleaved~~, ~~amino terminal domain~~ of ~~apolipoprotein E3~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased~~ Structures]]	+	</div>
-	[[Category: ~~Mcpherson~~, A]]	+	<div class="pdbe-citations 6v7m" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: McPherson, A]]
		+	[[Category: Alzheimer]]
		+	[[Category: Disease]]
		+	[[Category: Lipid]]
		+	[[Category: Lipid transport]]
		+	[[Category: Lipoprotein]]
		+	[[Category: Proteolysis]]

OCA: Protected "6v7m" [edit=sysop:move=sysop]

2019-12-18T06:04:24Z

Protected "6v7m" [edit=sysop:move=sysop]

←Older revision

Revision as of 06:04, 18 December 2019

OCA: New page: '''Unreleased structure''' The entry 6v7m is ON HOLD Authors: McPherson, A. Description: Crystal structure of a proteolytically cleaved, amino terminal domain of apolipoprotein E3 [[Ca...

2019-12-18T06:04:22Z

New page: '''Unreleased structure''' The entry 6v7m is ON HOLD Authors: McPherson, A. Description: Crystal structure of a proteolytically cleaved, amino terminal domain of apolipoprotein E3 [[Ca...

New page

'''Unreleased structure'''

The entry 6v7m is ON HOLD

Authors: McPherson, A.

Description: Crystal structure of a proteolytically cleaved, amino terminal domain of apolipoprotein E3
[[Category: Unreleased Structures]]
[[Category: Mcpherson, A]]