SASDDA8: Apolipoprotein E4 (ApoE4)

Basic information

Entry

Database: SASBDB / ID: SASDDA8

Sample

Apolipoprotein E4

• Apolipoprotein E4 (protein), ApoE4, Homo sapiens

Function / homology

Function:

positive regulation of heparan sulfate proteoglycan binding / lipid transport involved in lipid storage / chylomicron remnant / intermediate-density lipoprotein particle clearance / positive regulation of lipid transport across blood-brain barrier / regulation of cellular response to very-low-density lipoprotein particle stimulus / positive regulation of low-density lipoprotein particle receptor catabolic process / metal chelating activity / triglyceride-rich lipoprotein particle clearance / lipoprotein particle / Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors / regulation of amyloid-beta clearance / negative regulation of cholesterol biosynthetic process / discoidal high-density lipoprotein particle / intermediate-density lipoprotein particle / chylomicron remnant clearance / maintenance of location in cell / very-low-density lipoprotein particle remodeling / very-low-density lipoprotein particle receptor binding / very-low-density lipoprotein particle clearance / Chylomicron clearance / NMDA glutamate receptor clustering / acylglycerol homeostasis / response to caloric restriction / Chylomicron remodeling / cellular response to lipoprotein particle stimulus / negative regulation of triglyceride metabolic process / phosphatidylcholine-sterol O-acyltransferase activator activity / positive regulation of phospholipid efflux / Chylomicron assembly / positive regulation of cholesterol metabolic process / regulation of amyloid fibril formation / regulation of behavioral fear response / regulation of protein metabolic process / high-density lipoprotein particle clearance / chylomicron / lipoprotein catabolic process / lipid transporter activity / high-density lipoprotein particle remodeling / phospholipid efflux / melanosome organization / multivesicular body, internal vesicle / AMPA glutamate receptor clustering / cholesterol transfer activity / reverse cholesterol transport / high-density lipoprotein particle assembly / positive regulation of amyloid-beta clearance / very-low-density lipoprotein particle / positive regulation by host of viral process / low-density lipoprotein particle / lipoprotein biosynthetic process / positive regulation of CoA-transferase activity / protein import / high-density lipoprotein particle / negative regulation of blood coagulation / low-density lipoprotein particle remodeling / negative regulation of amyloid fibril formation / heparan sulfate proteoglycan binding / synaptic transmission, cholinergic / regulation of Cdc42 protein signal transduction / amyloid precursor protein metabolic process / regulation of amyloid precursor protein catabolic process / cholesterol catabolic process / triglyceride homeostasis / positive regulation of membrane protein ectodomain proteolysis / negative regulation of protein metabolic process / HDL remodeling / triglyceride metabolic process / negative regulation of endothelial cell migration / Scavenging by Class A Receptors / cholesterol efflux / low-density lipoprotein particle receptor binding / artery morphogenesis / regulation of axon extension / regulation of cholesterol metabolic process / positive regulation of amyloid fibril formation / virion assembly / positive regulation of dendritic spine development / regulation of innate immune response / negative regulation of amyloid-beta formation / negative regulation of endothelial cell proliferation / locomotory exploration behavior / regulation of neuronal synaptic plasticity / antioxidant activity / lipoprotein particle binding / positive regulation of endocytosis / response to dietary excess / negative regulation of blood vessel endothelial cell migration / negative regulation of long-term synaptic potentiation / negative regulation of protein secretion / positive regulation of dendritic spine maintenance / negative regulation of platelet activation / positive regulation of cholesterol efflux / regulation of protein-containing complex assembly / intracellular transport / fatty acid homeostasis / long-term memory / long-chain fatty acid transport / positive regulation of lipid biosynthetic process / regulation of proteasomal protein catabolic process

Domain/homology:

Apolipoprotein A/E / : / Apolipoprotein A1/A4/E domain

Component:

Apolipoprotein E

• 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-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.

Contact author

• Lucas Kraft (University of Sussex)

Models

Sample

• Sample: Name: Apolipoprotein E4
• Buffer: Name: 20 mM HEPES, 300 mM NaCl / pH: 8

Entity #1109

Name: ApoE4 / Type: protein / Description: Apolipoprotein E4 / Formula weight: 34.712 / Num. of mol.: 4 / Source: Homo sapiens / References: UniProt: P02649
Sequence:

GPHMKVEQAV ETEPEPELRQ QTEWQSGQRW ELALGRFWDY LRWVQTLSEQ VQEELLSSQV TQELRALMDE TMKELKAYKS ELEEQLTPVA EETRARLSKE LQAAQARLGA DMEDVRGRLV QYRGEVQAML GQSTEELRVR LASHLRKLRK RLLRDADDLQ KRLAVYQAGA 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 synchrotron / Wavelength: 0.1 Å / Dist. spec. to detc.: 3.9 mm
• Detector: Name: Pilatus 2M

Scan

Title: Apolipoprotein E4 / Measurement date: Nov 29, 2017 / Storage temperature: 4 °C / Cell temperature: 20 °C / Exposure time: 3 sec. / Number of frames: 1 / Unit: 1/A /

	Min	Max
Q	0.0034	0.3696

Distance distribution function P(R)

Sofotware P(R): GNOM 4.6 / Number of points: 347 /

	Min	Max
Q	0.00585	0.235
P(R) point	11	357
R	0	195.5

Result

Type of curve: sec / Comments: Concentration UNKNOWN. /

	Experimental	Porod
MW	127 kDa	-
Volume	-	430 nm3

	P(R)	Guinier	Guinier error
Forward scattering, I0	0.2411	0.2394	0.0063
Radius of gyration, Rg	5.93 nm	5.769 nm	0.066

	Min	Max
D	-	19.55
Guinier point	11	88