Apolipoprotein A-I (apoA-I) is an exchangeable apolipoprotein that constitutes the major protein component of high density cholesterol. ApoA-I is a two-domain protein comprising an N-terminal helix bundle and a less-structured C-terminal domain in the lipid-free state. In the present study, the contribution of the C-terminal domain to the lipid binding and antimicrobial activity of apoA-I was investigated using a chimeric construct in which the C-terminal domain of apoA-I (179-243) was attached to an insect apolipoprotein, Locusta migratoria apolipophorin III (apoLp-III), bearing cysteine substitutions for residues 20 and 149. Circular dichroism results were consistent with the addition of a poorly structured domain to apoLp-III and revealed the apoLp-III helix bundle was successfully closed under oxidizing conditions. Electrophoresis, fluorescence spectroscopy and an in vitro study using macrophage cells revealed that the C-terminal domain in itself was insufficient for efficient binding to lipid, lipopolysaccharide and phosphatidylglycerol vesicles. These results suggest the underlying mechanisms governing these interactions are potentiated by cooperativity between the N- and C-terminal domains of apoA-I.
|Commitee:||Narayanaswami, Vasanthy, Schwans, Jason|
|School:||California State University, Long Beach|
|Department:||Chemistry and Biochemistry|
|School Location:||United States -- California|
|Source:||MAI 56/01M(E), Masters Abstracts International|
|Keywords:||Apolipoprotein A-I, C-terminal domain, High density cholesterol|
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