| Summary: | 碩士 === 國立中正大學 === 分子生物研究所 === 99 === Abstract
Apolipoprotein E (ApoE) is a plasma apolipoprotein of 299-amino acid (34kDa) that is mainly synthesized in liver. ApoE plays an important role in lipoprotein transport and cholesterol clearance. ApoE also produced and secreted by the brain is implicated in neuronal regeneration. Previous study has shown that ApoE contains two structural domains, a 22 kDa NH2-terminal (residues 1-191) and a 10 kDa COOH-terminal domains (residues 216-299). These two domains are separated by a flexible hinge region. The NH2-terminal domain containing the lipoprotein receptor binding region consists of a four-helix bundle with antiparallel arrangement. The COOH-terminal domain contains the lipoprotein (lipid) binding site. The structure of the COOH-terminal domain remains unknown, but is predicted to be highly amphipathic α-helices. Three major common isoforms of ApoE in human, ApoE2, ApoE3, and ApoE4, have been identified. Recent studies have revealed that ApoE interacts with senile plaques in the brains of the patients with Alzheimer disease. ApoE4 is a major risk factor for Alzheimer’s disease and atherosclerosis. ApoE has been shown that the domain interaction influences its biochemical and metabolic properties. Up to now, the three-dimensional structures of N-terminal domain of ApoE isoforms have been solved by X-ray crystallography and NMR spectroscopy, but the structural properties of intact ApoE isoforms are largely unknown. In this study, we focused on the structural characterization of the COOH-terminal domain of ApoE and I prepared the ApoE(222-271) and (222-299) for structural analysis by NMR.
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