+Open data
-Basic information
Entry | Database: SASBDB / ID: SASDDD7 |
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Sample | Apolipoprotein E2
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Function / homology | Function and homology information chylomicron remnant / lipid transport involved in lipid storage / triglyceride-rich lipoprotein particle clearance / intermediate-density lipoprotein particle clearance / positive regulation of lipid transport across blood-brain barrier / positive regulation of heparan sulfate proteoglycan binding / regulation of cellular response to very-low-density lipoprotein particle stimulus / metal chelating activity / Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors / discoidal high-density lipoprotein particle ...chylomicron remnant / lipid transport involved in lipid storage / triglyceride-rich lipoprotein particle clearance / intermediate-density lipoprotein particle clearance / positive regulation of lipid transport across blood-brain barrier / positive regulation of heparan sulfate proteoglycan binding / regulation of cellular response to very-low-density lipoprotein particle stimulus / metal chelating activity / Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors / discoidal high-density lipoprotein particle / chylomicron remnant clearance / lipoprotein particle / maintenance of location in cell / very-low-density lipoprotein particle clearance / intermediate-density lipoprotein particle / very-low-density lipoprotein particle remodeling / regulation of amyloid-beta clearance / response to caloric restriction / Chylomicron clearance / negative regulation of triglyceride metabolic process / NMDA glutamate receptor clustering / chylomicron / Chylomicron remodeling / phosphatidylcholine-sterol O-acyltransferase activator activity / positive regulation of phospholipid efflux / Chylomicron assembly / lipid transporter activity / positive regulation of low-density lipoprotein particle receptor catabolic process / positive regulation of cholesterol metabolic process / regulation of behavioral fear response / high-density lipoprotein particle remodeling / high-density lipoprotein particle clearance / multivesicular body, internal vesicle / lipoprotein catabolic process / very-low-density lipoprotein particle receptor binding / phospholipid efflux / regulation of amyloid fibril formation / regulation of protein metabolic process / AMPA glutamate receptor clustering / low-density lipoprotein particle / positive regulation by host of viral process / cholesterol transfer activity / reverse cholesterol transport / positive regulation of amyloid-beta clearance / high-density lipoprotein particle assembly / very-low-density lipoprotein particle / positive regulation of CoA-transferase activity / melanosome organization / lipoprotein biosynthetic process / protein import / negative regulation of blood coagulation / low-density lipoprotein particle remodeling / high-density lipoprotein particle / negative regulation of amyloid fibril formation / negative regulation of cholesterol biosynthetic process / amyloid precursor protein metabolic process / heparan sulfate proteoglycan binding / regulation of Cdc42 protein signal transduction / triglyceride homeostasis / regulation of amyloid precursor protein catabolic process / cholesterol catabolic process / synaptic transmission, cholinergic / positive regulation of membrane protein ectodomain proteolysis / HDL remodeling / negative regulation of endothelial cell migration / cholesterol efflux / Scavenging by Class A Receptors / negative regulation of protein metabolic process / artery morphogenesis / triglyceride metabolic process / regulation of axon extension / regulation of cholesterol metabolic process / positive regulation of amyloid fibril formation / low-density lipoprotein particle receptor binding / positive regulation of dendritic spine development / virion assembly / regulation of innate immune response / regulation of neuronal synaptic plasticity / locomotory exploration behavior / lipoprotein particle binding / positive regulation of endocytosis / negative regulation of amyloid-beta formation / negative regulation of endothelial cell proliferation / antioxidant activity / cGMP-mediated signaling / response to dietary excess / negative regulation of blood vessel endothelial cell migration / negative regulation of long-term synaptic potentiation / negative regulation of platelet activation / positive regulation of cholesterol efflux / positive regulation of dendritic spine maintenance / intracellular transport / regulation of protein-containing complex assembly / negative regulation of protein secretion / long-term memory / fatty acid homeostasis / long-chain fatty acid transport / positive regulation of lipid biosynthetic process / synaptic cleft / regulation of proteasomal protein catabolic process Similarity search - Function |
Biological species | Homo sapiens (human) |
Citation | Journal: J Mol Biol / Year: 2019 Title: The Molecular Basis for Apolipoprotein E4 as the Major Risk Factor for Late-Onset Alzheimer's Disease. Authors: Ana-Caroline Raulin / Lucas Kraft / Youssra K Al-Hilaly / Wei-Feng Xue / John E McGeehan / John R Atack / Louise Serpell / Abstract: Apolipoprotein E4 (ApoE4) is one of three (E2, E3 and E4) human isoforms of an α-helical, 299-amino-acid protein. Homozygosity for the ε4 allele is the major genetic risk factor for developing late- ...Apolipoprotein E4 (ApoE4) is one of three (E2, E3 and E4) human isoforms of an α-helical, 299-amino-acid protein. Homozygosity for the ε4 allele is the major genetic risk factor for developing late-onset Alzheimer's disease (AD). ApoE2, ApoE3 and ApoE4 differ at amino acid positions 112 and 158, and these sequence variations may confer conformational differences that underlie their participation in the risk of developing AD. Here, we compared the shape, oligomerization state, conformation and stability of ApoE isoforms using a range of complementary biophysical methods including small-angle x-ray scattering, analytical ultracentrifugation, circular dichroism, x-ray fiber diffraction and transmission electron microscopy We provide an in-depth and definitive study demonstrating that all three proteins are similar in stability and conformation. However, we show that ApoE4 has a propensity to polymerize to form wavy filaments, which do not share the characteristics of cross-β amyloid fibrils. Moreover, we provide evidence for the inhibition of ApoE4 fibril formation by ApoE3. This study shows that recombinant ApoE isoforms show no significant differences at the structural or conformational level. However, self-assembly of the ApoE4 isoform may play a role in pathogenesis, and these results open opportunities for uncovering new triggers for AD onset. |
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-Structure visualization
-Downloads & links
-Data source
SASBDB page | SASDDD7 |
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-Related structure data
Related structure data | C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-External links
Related items in Molecule of the Month |
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-Models
-Sample
Sample | Name: Apolipoprotein E2 |
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Buffer | Name: 20 mM HEPES, 300 mM NaCl / pH: 8 |
Entity #1086 | Name: ApoE2 / Type: protein / Description: Apolipoprotein E2 / Formula weight: 34.606 / Num. of mol.: 4 / Source: Homo sapiens / References: UniProt: P02649 Sequence: GPHMKVEQAV ETEPEPELRQ QTEWQSGQRW ELALGRFWDY LRWVQTLSEQ VQEELLSSQV TQELRALMDE TMKELKAYKS ELEEQLTPVA EETRARLSKE LQAAQARLGA DMEDVCGRLV QYRGEVQAML GQSTEELRVR LASHLRKLRK RLLRDADDLQ KCLAVYQAGA ...Sequence: GPHMKVEQAV ETEPEPELRQ QTEWQSGQRW ELALGRFWDY LRWVQTLSEQ VQEELLSSQV TQELRALMDE TMKELKAYKS ELEEQLTPVA EETRARLSKE LQAAQARLGA DMEDVCGRLV QYRGEVQAML GQSTEELRVR LASHLRKLRK RLLRDADDLQ KCLAVYQAGA REGAERGLSA IRERLGPLVE QGRVRAATVG SLAGQPLQER AQAWGERLRA RMEEMGSRTR DRLDEVKEQV AEVRAKLEEQ AQQIRLQAEA FQARLKSWFE PLVEDMQRQW AGLVEKVQAA VGTSAAPVPS DNH |
-Experimental information
Beam | Instrument name: Diamond Light Source B21 / City: Oxfordshire / 国: UK / Shape: 1 x 5 mm / Type of source: X-ray synchrotronSynchrotron / Wavelength: 0.1 Å / Dist. spec. to detc.: 3.9 mm | ||||||||||||||||||||||||||||||
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Detector | Name: Pilatus 2M | ||||||||||||||||||||||||||||||
Scan | Title: Apolipoprotein E2 / Measurement date: Nov 29, 2017 / Storage temperature: 4 °C / Cell temperature: 20 °C / Exposure time: 3 sec. / Number of frames: 7 / Unit: 1/A /
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Distance distribution function P(R) | Sofotware P(R): GNOM 4.6 / Number of points: 367 /
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Result | Type of curve: sec Comments: Sample concentration: UNKNOWN. The experimental molecular weight (MW) quoted in this entry (144 kDa) was determined using multi-angle laser light scattering (MALLS). Analytical ...Comments: Sample concentration: UNKNOWN. The experimental molecular weight (MW) quoted in this entry (144 kDa) was determined using multi-angle laser light scattering (MALLS). Analytical ultracentrifugation provides a MW estimate of 122 kDa.
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