Deletion of amino acids Glu146-->Arg160 in human apolipoprotein A-I (ApoA-ISeattle) alters lecithin:cholesterol acyltransferase activity and recruitment of cell phospholipid.

摘要: Human apolipoprotein A-I (apoA-I) has an important role in the efflux of cholesterol from peripheral cells, first step reverse transport. Deletion amino acids Glu146-->Arg160 apoA-I (apoA-ISeattle) removes a large section lipid binding helix and is associated vivo with atherogenic lipoprotein profile characterized by deficiency high-density lipoproteins (HDL). In present study, we asked whether apoA-ISeattle had normal ability to recruit lipids cells form nascent (HDL) particles altered secondary structure affected lecithin:cholesterol acyltransferase (LCAT) activity. Wild-type expressed transfected Chinese hamster ovary formed HDL similar density distribution protein-to-lipid ratio. Phospholipid subclass demonstrated significant increase sphingomyelin phosphatidylethanolamine compared wild type. ApoA-ISeattle unique size wild-type HDL; (9-20 nm) predominated while there were virtually no small (7.5 particles. LCAT reactivity was impaired where esterification only half that complexes. The conformation on studied panel monoclonal antibodies (Mabs) specific for apoA-I. Mabs recognize putative activation site, residues 95-122, reactivity. As expected, recognized 141-164 unreactive because 146-160 deletion; addition, low Mab recognizes 220-242. data suggest and/or 220-242 partake cooperative interactions between helices may be maximal esterification.