Structural variation in human apolipoprotein E3 and E4: Secondary structure, tertiary structure, and size distribution

Chi Yuan Chou, Yi Ling Lin, Yu Chyi Huang, Sheh Yi Sheu, Ta Hsien Lin, Huey Jen Tsay, Gu Gang Chang*, Ming Shi Shiao

*此作品的通信作者

研究成果: Article同行評審

38 引文 斯高帕斯(Scopus)

摘要

Human apolipoprotein E (apoE) is a 299-amino-acid protein with a molecular weight of 34 kDa. The difference between the apoE3 and apoE4 isoforms is a single residue substitution involving a Cys-Arg replacement at residue 112. ApoE4 is positively associated with atherosclerosis and late-onset and sporadic Alzheimer's disease (AD). ApoE4 and its C-terminal truncated fragments have been found in the senile plaques and neurofibrillary tangles in the brain of AD patients. However, detail structural information regarding isoform and domain interaction remains poorly understood. We prepared full-length, N-, and C-terminal truncated apoE3 and apoE4 proteins and studied their structural variation. Sedimentation velocity and continuous size distribution analysis using analytical ultracentrifugation revealed apoE372-299 as consisting of a major species with a sedimentation coefficient of 5.9. ApoE472-299 showed a wider and more complicated species distribution. Both apoE3 and E4 N-terminal domain (1-191) existed with monomers as the major component together with some tetramer. The oligomerization and aggregation of apoE protein increased when the C-terminal domain (192-271) was incorporated. The structural influence of the C-terminal domain on apoE is to assist self-association with no significant isoform preference. Circular dichroism and fluorescence studies demonstrated that apoE472-299 possessed a more α-helical structure with more hydrophobic residue exposure. The structural variation of the N-terminal truncated apoE3 and apoE4 protein provides useful information that helps to explain the greater aggregation of the apoE4 isoform and thus has implication for the involvement of apoE4 in AD.

原文English
頁(從 - 到)455-466
頁數12
期刊Biophysical Journal
88
發行號1
DOIs
出版狀態Published - 1月 2005

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