Apolipoprotein E includes a binding site which is recognized by several amyloidogenic polypeptides.

Apolipoprotein E includes a binding site which is recognized by several amyloidogenic polypeptides.
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载脂蛋白E包括被几种淀粉样蛋白生成多肽识别的结合位点。

DOI:
10.1042/0264-6021:3490077
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发表时间:
2000
期刊:
The Biochemical journal
影响因子:
--
通讯作者:
Haltia,M
Haltia,M
中科院分区:
--
文献类型:
--
作者:
Baumann,MH;Kallijärvi,J;Lankinen,H;Soto,C;Haltia,M

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载脂蛋白E (apoE) ϵ4等位基因的遗传是迟发性阿尔茨海默病(AD)的危险因素。生物化学上apoE存在于AD斑块和AD脑的神经原纤维缠结中。apoE与淀粉样蛋白β-肽(a β)具有高度的亲和性和特异性结合。除AD外,apoE也存在于许多其他脑和全身性淀粉样病变、唐氏综合征和朊病毒疾病中,但其存在的病理生理基础尚不清楚。在本研究中,我们比较了apoE与Aβ、凝胶来源的淀粉样蛋白片段agel183 -210和淀粉样蛋白片段prp109 -122和PrP109-141的相互作用。我们发现,与a β类似,AGel和PrP片段也可以与apoE形成复合物,并且apoE与淀粉样蛋白片段之间的相互作用是通过apoE上相同的结合位点介导的。我们还发现,apoE增加了PrP和AGel的硫黄素- t荧光,并且apoE影响了这些淀粉样蛋白片段的β-片构象的含量。我们的研究结果表明,淀粉样蛋白和淀粉样朊病毒片段具有相似的结构基序,该基序可能通过单一结合位点被apoE识别,并且该基序也负责这些片段的淀粉样变性。
Inheritance of the apolipoprotein E (apoE) ϵ4 allele is a risk factor for late-onset Alzheimer's disease (AD). Biochemically apoE is present in AD plaques and neurofibrillary tangles of the AD brain. There is a high avidity and specific binding of apoE and the amyloid β-peptide (Aβ). In addition to AD apoE is also present in many other cerebral and systemic amyloidoses, Down's syndrome and prion diseases but the pathophysiological basis for its presence is still unknown. In the present study we have compared the interaction of apoE with Aβ, the gelsolin-derived amyloid fragment AGel183-210and the amyloidogenic prion fragments PrP109-122and PrP109-141. We show that, similar to Aβ, also AGel and PrP fragments can form a complex with apoE, and that the interaction between apoE and the amyloidogenic protein fragments is mediated through the same binding site on apoE. We also show that apoE increases the thioflavin-T fluorescence of PrP and AGel and that apoE influences the content of β-sheet conformation of these amyloidogenic fragments. Our results indicate that amyloids and amyloidogenic prion fragments share a similar structural motif, which is recognized by apoE, possibly through a single binding site, and that this motif is also responsible for the amyloidogenicity of these fragments.
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影响因子: 3.1
作者:
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影响因子: --
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DOI: --
发表时间: 1993
期刊: The Lancet
影响因子: --
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