SASDDA8: Apolipoprotein E4 (ApoE4)

基本情報

登録情報

データベース: SASBDB / ID: SASDDA8

試料

Apolipoprotein E4

• Apolipoprotein E4 (protein), ApoE4, Homo sapiens

機能・相同性

分子機能:

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 / 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 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 / positive regulation of low-density lipoprotein particle receptor catabolic process / 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 / very-low-density lipoprotein particle receptor binding / 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 / cholesterol catabolic process / triglyceride homeostasis / regulation of amyloid precursor protein catabolic process / positive regulation of membrane protein ectodomain proteolysis / negative regulation of protein metabolic process / HDL remodeling / negative regulation of endothelial cell migration / cholesterol efflux / Scavenging by Class A Receptors / artery morphogenesis / regulation of axon extension / regulation of cholesterol metabolic process / triglyceride metabolic process / low-density lipoprotein particle receptor binding / positive regulation of amyloid fibril formation / positive regulation of dendritic spine development / regulation of innate immune response / virion assembly / negative regulation of endothelial cell proliferation / negative regulation of amyloid-beta formation / locomotory exploration behavior / antioxidant activity / regulation of neuronal synaptic plasticity / 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 / positive regulation of dendritic spine maintenance / negative regulation of platelet activation / positive regulation of cholesterol efflux / regulation of protein-containing complex assembly / intracellular transport / negative regulation of protein secretion / fatty acid homeostasis / long-term memory / long-chain fatty acid transport / positive regulation of lipid biosynthetic process / Retinoid metabolism and transport

ドメイン・相同性:

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

構成要素:

Apolipoprotein E

• 生物種: Homo sapiens (ヒト)
• 引用: ジャーナル: J Mol Biol / 年: 2019; タイトル: The Molecular Basis for Apolipoprotein E4 as the Major Risk Factor for Late-Onset Alzheimer's Disease.; 著者: Ana-Caroline Raulin / Lucas Kraft / Youssra K Al-Hilaly / Wei-Feng Xue / John E McGeehan / John R Atack / Louise Serpell / ; 要旨: 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.

登録者

• Lucas Kraft (University of Sussex)

モデル

試料

• 試料: 名称: Apolipoprotein E4
• バッファ: 名称: 20 mM HEPES, 300 mM NaCl / pH: 8

要素 #1109

名称: ApoE4 / タイプ: protein / 記述: Apolipoprotein E4 / 分子量: 34.712 / 分子数: 4 / 由来: Homo sapiens / 参照: UniProt: P02649
配列:

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

実験情報

• ビーム: 設備名称: Diamond Light Source B21 / 地域: Oxfordshire / 国: UK / 形状: 1 x 5 mm / 線源: X-ray synchrotron / 波長: 0.1 Å / スペクトロメータ・検出器間距離: 3.9 mm
• 検出器: 名称: Pilatus 2M

スキャン

タイトル: Apolipoprotein E4 / 測定日: 2017年11月29日 / 保管温度: 4 °C / セル温度: 20 °C / 照射時間: 3 sec. / フレーム数: 1 / 単位: 1/A /

	Min	Max
Q	0.0034	0.3696

距離分布関数 P(R)

ソフトウェア P(R): GNOM 4.6 / ポイント数: 347 /

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

結果

カーブのタイプ: sec / コメント: Concentration UNKNOWN. /

	実験値	Porod
分子量	127 kDa	-
体積	-	430 nm3

	P(R)	Guinier	Guinier error
前方散乱 I0	0.2411	0.2394	0.0063
慣性半径, Rg	5.93 nm	5.769 nm	0.066

	Min	Max
D	-	19.55
Guinier point	11	88