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

被引:31
作者
Baumann, MH
Kallijärvi, J
Lankinen, H
Soto, C
Haltia, M
机构
[1] Inst Biomed, Prot Chem Educ & Res Unit, FIN-00014 Helsinki, Finland
[2] Haartman Inst, Dept Virol, Peptide & Prot Lab, FIN-00014 Helsinki, Finland
[3] Univ Helsinki, Haartman Inst, Dept Pathol, FIN-00014 Helsinki, Finland
关键词
Alzheimer's disease; amyloidosis of the Finnish type; pathological chaperone; prion disease;
D O I
10.1042/0264-6021:3490077
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Inheritance of the apolipoprotein E (apoE) epsilon 4 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 beta-peptide (A beta). 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 A beta, the gelsolin-derived amyloid fragment AGel(183-210) and the amyloidogenic prion fragments PrP100-122 and PrP100-141. We show that, similar to A beta, 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 beta-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.
引用
收藏
页码:77 / 84
页数:8
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