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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Structural differences between apoE3 and apoE4 may be useful in developing therapeutic agents for Alzheimer's disease
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Structural differences between apoE3 and apoE4 may be useful in developing therapeutic agents for Alzheimer's disease

机译：apoE3和apoE4之间的结构差异可能有助于开发治疗阿尔茨海默氏病的药物

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摘要

Apolipoproteins E3 and E4, proteins with a molecular mass of 34.15 kDa, differ by a single amino acid change. ApoE4 contains an arginine residue at position 112, whereas apoE3 has a cysteine at this position. ApoE4 is the major risk factor for late-onset Alzheimer's disease, whereas apoE3, the common isoform, is neutral with respect to this disease. Here, using literature data from both hydrogen-deuterium exchange and site-directed mutations, we suggest structural differences between these two isoforms that are distant from the site of the arginine-to-cysteine change. These structural differences involve sequences from both the N- and C-terminal domains, sequentially far apart but structurally close. In addition, these regions are close to regions that bind lipid and to a region involved in association of apoE monomers to higher molecular weight forms. We discuss the possibility that these regions could be targeted preferentially to affect the function of apoE4 relative to apoE3.
机译：载脂蛋白E3和E4是分子量为34.15 kDa的蛋白质，它们的区别在于单个氨基酸变化。 ApoE4在位置112处含有一个精氨酸残基，而apoE3在此位置处有一个半胱氨酸。 ApoE4是晚期阿尔茨海默氏病的主要危险因素，而常见的亚型apoE3对这种疾病是中性的。在这里，使用来自氢-氘交换和定点突变的文献数据，我们建议这两个同工型之间的结构差异与精氨酸到半胱氨酸变化的位置相距甚远。这些结构差异涉及来自N端和C端结构域的序列，顺序相距较远，但结构上较近。另外，这些区域靠近结合脂质的区域，并且靠近apoE单体与较高分子量形式缔合所涉及的区域。我们讨论了可能优先针对这些区域影响apoE4相对于apoE3的功能的可能性。

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