SASDDD7: Apolipoprotein E2 (ApoE2)

基本情報

登録情報

データベース: SASBDB / ID: SASDDD7

試料

Apolipoprotein E2

• Apolipoprotein E2 (protein), ApoE2, Homo sapiens

機能・相同性

分子機能:

lipid transport involved in lipid storage / 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 / discoidal high-density lipoprotein particle / lipoprotein particle / negative regulation of triglyceride metabolic process / negative regulation of cholesterol biosynthetic process / regulation of amyloid-beta clearance / positive regulation of lipoprotein transport / Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors / chylomicron remnant clearance / chylomicron remnant / intermediate-density lipoprotein particle / maintenance of location in cell / very-low-density lipoprotein particle remodeling / acylglycerol homeostasis / NMDA glutamate receptor clustering / response to caloric restriction / phosphatidylcholine-sterol O-acyltransferase activator activity / Chylomicron clearance / positive regulation of phospholipid efflux / very-low-density lipoprotein particle clearance / Chylomicron remodeling / lipid transporter activity / positive regulation of cholesterol metabolic process / regulation of behavioral fear response / cellular response to lipoprotein particle stimulus / positive regulation of low-density lipoprotein particle receptor catabolic process / regulation of amyloid fibril formation / Chylomicron assembly / : / high-density lipoprotein particle clearance / chylomicron / phospholipid efflux / regulation of protein metabolic process / high-density lipoprotein particle remodeling / very-low-density lipoprotein particle receptor binding / AMPA glutamate receptor clustering / lipoprotein catabolic process / melanosome organization / multivesicular body, internal vesicle / reverse cholesterol transport / positive regulation of amyloid-beta clearance / positive regulation by host of viral process / high-density lipoprotein particle assembly / low-density lipoprotein particle / protein import / lipoprotein biosynthetic process / cholesterol transfer activity / high-density lipoprotein particle / very-low-density lipoprotein particle / cholesterol catabolic process / low-density lipoprotein particle remodeling / heparan sulfate proteoglycan binding / regulation of Cdc42 protein signal transduction / amyloid precursor protein metabolic process / negative regulation of amyloid fibril formation / triglyceride homeostasis / regulation of amyloid precursor protein catabolic process / positive regulation of membrane protein ectodomain proteolysis / synaptic transmission, cholinergic / HDL remodeling / negative regulation of endothelial cell migration / cholesterol efflux / regulation of axon extension / regulation of cholesterol metabolic process / negative regulation of protein metabolic process / artery morphogenesis / Scavenging by Class A Receptors / triglyceride metabolic process / positive regulation of dendritic spine development / low-density lipoprotein particle receptor binding / positive regulation of amyloid fibril formation / regulation of innate immune response / virion assembly / negative regulation of amyloid-beta formation / negative regulation of endothelial cell proliferation / locomotory exploration behavior / antioxidant activity / positive regulation of endocytosis / lipoprotein particle binding / response to dietary excess / negative regulation of blood vessel endothelial cell migration / regulation of neuronal synaptic plasticity / negative regulation of long-term synaptic potentiation / negative regulation of platelet activation / positive regulation of dendritic spine maintenance / negative regulation of blood coagulation / positive regulation of cholesterol efflux / negative regulation of MAP kinase activity / long-term memory / negative regulation of protein secretion / fatty acid homeostasis / regulation of protein-containing complex assembly / synaptic cleft / long-chain fatty acid transport / intracellular 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 E2
• バッファ: 名称: 20 mM HEPES, 300 mM NaCl / pH: 8

要素 #1086

名称: ApoE2 / タイプ: protein / 記述: Apolipoprotein E2 / 分子量: 34.606 / 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 DMEDVCGRLV QYRGEVQAML GQSTEELRVR LASHLRKLRK RLLRDADDLQ KCLAVYQAGA 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 E2 / 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: 7 / 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: 367 /

	Min	Max
Q	0.008942	0.2513
P(R) point	23	389
R	0	194.5

結果

カーブのタイプ: sec
コメント: 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.

	実験値	Porod
分子量	144 kDa	-
体積	-	400 nm3

	P(R)	Guinier	Guinier error
前方散乱 I0	0.2785	0.276	0.00049
慣性半径, Rg	5.82 nm	5.634 nm	0.063

	Min	Max
D	-	19.45
Guinier point	22	89