ATP-binding cassette transporter A-1 (
ABCA1)-
mediated lipid
efflux to lipid-poor apolipoprotein A-I (apoA-I) results in the gradual lipidation of apoA-I. This leads to the formation of discoidalhigh-density lipoproteins (HDL), which are subsequently converted to spherical HDL by the action oflecithin:
cholesterol acyltransferase (LCAT). We have investigated the effect of point mutations and deletionsin the carboxy-terminal region of apoA-I on the biogenesis of HDL using adenovirus-
mediated gene transferin apoA-I-deficient mice. It was found that the plasma HDL levels were greatly reduced in mice expressingthe carboxy-terminal deletion mutants apoA-I[
![](/images/gifchars/Delta.gif)
(185-243)] and apoA-I[
![](/images/gifchars/Delta.gif)
(220-243)], shown previouslyto diminish the ABCA1-
mediated lipid
efflux. The HDL levels were normal in mice expressing the WTapoA-I, the apoA-I[
![](/images/gifchars/Delta.gif)
(232-243)] deletion mutant, or the apoA-I[E191A/H193A/K195A] point mutant,which promote normal ABCA1-
mediated lipid
efflux. Electron microscopy and two-dimensional gelelectrophoresis showed that the apoA-I[
![](/images/gifchars/Delta.gif)
(185-243)] and apoA-I[
![](/images/gifchars/Delta.gif)
(220-243)] mutants formed mainlypre
![](/images/gifchars/beta2.gif)
-HDL particles and few spherical particles enriched in apoE, while WT apoA-I, apoA-I[
![](/images/gifchars/Delta.gif)
(232-243)], and apoA-I[E191A/H193A/K195A] formed spherical
![](/images/gifchars/alpha.gif)
-HDL particles. The findings establish that(a) deletions that eliminate the 220-231 region of apoA-I prevent the synthesis of
![](/images/gifchars/alpha.gif)
-HDL but allow thesynthesis of pre
![](/images/gifchars/beta2.gif)
-HDL particles in vivo, (b) the amino-terminal segment 1-184 of apoA-I can promotesynthesis of pre
![](/images/gifchars/beta2.gif)
-HDL-type particles in an ABCA1-independent process, and (c) the charged residues inthe 191-195 region of apoA-I do not influence the biogenesis of HDL.