Apolipoprotein E3 (apoE3) is a 299 residue exchangeable apolipoprotein that has the ability to exist in lipid-free and lipoprotein-bound state. It plays a crucial role as an anti-atherogenic agent by removing cholesterol and triglycerides from circulation via the low-density lipoprotein receptor family of proteins. It also functions in reverse cholesterol transport in atherosclerosis by promoting cholesterol efflux from macrophages, a process that leads to the initial formation of nascent discoidal high-density lipoproteins (nHDL) composed of a bilayer of lipids surrounded by apoE3.
The objective of this study is to examine the molecular organization of apoE3 in HDL. Reconstituted HDL (rHDL) was prepared using single Cys variants of apoE3 (1-299) and synthetic phospholipids of physiological relevance. Pyrene fluorescence spectroscopy and Cys specific cross-linking studies were carried out to determine the spatial proximity of specified sites on neighboring apoE3 molecules in rHDL. Our results indicate that regardless of the location of the Cys residue, there was a decrease in excimer emission and absence of cross linker-mediated dimer in rHDL suggesting, that two apoE3 molecules are aligned in an anti- parallel fashion with respect to each other around the phospholipid bilayer. Our study offers new insights into the conformation of lipid-associated apoE3 in nascent HDL particles generated by macrophages, a critical step in atherosclerosis and cardiovascular disease.
|Commitee:||Shon, Young Seok, Weers, Paul M.M.|
|School:||California State University, Long Beach|
|Department:||Chemistry and Biochemistry|
|School Location:||United States -- California|
|Source:||MAI 55/05M(E), Masters Abstracts International|
|Keywords:||Apolipoprotein e, Cross-linking, High-density lipoprotein, Lipoprotein, Pyrene, Reverse cholesterol transport|
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