View source for 1oeg


==PEPTIDE OF HUMAN APOE RESIDUES 267-289, NMR, 5 STRUCTURES AT PH 6.0, 37 DEGREES CELSIUS AND PEPTIDE:SDS MOLE RATIO OF 1:90==
<StructureSection load='1oeg' size='340' side='right'caption='[[1oeg]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[1oeg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1OEG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1OEG FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=1oeg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1oeg OCA], [https://pdbe.org/1oeg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1oeg RCSB], [https://www.ebi.ac.uk/pdbsum/1oeg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1oeg ProSAT]</span></td></tr>
</table>
== Disease ==
[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 APOE*2 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 APOE*4 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 APOE*4 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 APOE*4 alleles in 42 families with late onset AD. Thus APOE*4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE*4 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 ==
[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.
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== Publication Abstract from PubMed ==
Structures of apoE(263-286) and apoE(267-289) have been determined in aqueous solution containing 90-fold molar excess of perdeuterated sodium dodecyl sulfate by CD and 1H NMR. Conformations were calculated by distance geometry based on 370 and 276 NOE distance restraints, respectively. RMSD for superimposing the region 265-284 from an ensemble of 41 structures for apoE(263-286) is 0.64 +/- 0.17 A for backbone atoms (N, C alpha, C = O) and 1.51 +/- 0.13 A for all atoms. The backbone RMSD for an ensemble of 37 structures for apoE(267-289) is 0.74 +/- 0.21 A for the region 268-275 and 0.34 +/- 0.10 A for the region 276-286. A two-domain structure was found for apoE(267-289) with the C-terminal half adopting a very well defined helix and the N-terminal segment 268-275 a less well defined helix, suggesting that the N-terminus may weakly bind to SDS. For apoE(263-286), an amphipathic helix-bend-helix structural motif was found with all hydrophobic side chains on the concave face. The existence of a bend around residues Q273 to G278 is consistent with their temperature coefficients of amide protons as well as secondary shifts of alpha-protons. Comparison of the structures of the two peptides revealed that the enhanced binding of apoE(263-286) to lipid could be attributed to the formation of a hydrophobic cluster consisting of residues W264, F265, L268, and V269. Aromatic side chains are proposed to be especially important in anchoring apolipoprotein fragments to micelles.

Conformations of human apolipoprotein E(263-286) and E(267-289) in aqueous solutions of sodium dodecyl sulfate by CD and 1H NMR.,Wang G, Pierens GK, Treleaven WD, Sparrow JT, Cushley RJ Biochemistry. 1996 Aug 13;35(32):10358-66. PMID:8756691<ref>PMID:8756691</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cushley RJ]]
[[Category: Pierens GK]]
[[Category: Sparrow JT]]
[[Category: Treleaven WD]]
[[Category: Wang G]]