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![]() | Apolipoprotein E2
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機能・相同性 | ![]() 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 / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() 類似検索 - 分子機能 |
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![]() | ![]() 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- ...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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![]() | 名称: Apolipoprotein E2 |
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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 ...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 ![]() ![]() ![]() | ||||||||||||||||||||||||||||||
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検出器 | 名称: Pilatus 2M | ||||||||||||||||||||||||||||||
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距離分布関数 P(R) |
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結果 | 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 ...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.
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