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J. Lipid Res.
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Journal of Lipid Research, Vol. 41, 1872-1882, November 2000
Copyright © 2000 by Lipid Research, Inc.


Original Article

Deletion of the propeptide of apolipoprotein A-I reduces protein expression but stimulates effective conversion of preß-high density lipoprotein to {alpha}-high density lipoprotein

Dmitri Sviridova, Louise E. Pylea, Matti Jauhiainenb, Christian Ehnholmb, and Noel H. Fidgea
a Baker Medical Research Institute, Melbourne, Victoria 8008, Australia
b Department of Biochemistry, National Public Health Institute, Helsinki, FIN-00300, Finland

Correspondence to: Dmitri Sviridov

The properties of the mature and pro-forms of recombinant apolipoprotein A-I (apoA-I) were compared with those of apoA-I isolated from human plasma. When the synthesis and secretion of pro- and mature forms of apoA-I from a baculovirus/insect cell expression system were compared in parallel experiments, the amount of the pro-form of apoA-I synthesized and secreted was severalfold higher than that of the mature form of apoA-I. A comparison of the properties of the pro- and mature forms of recombinant apoA-I and human plasma apoA-I showed no difference between all three in their secondary structure, their ability to self-associate, lipid-binding capacity, lecithin: cholesterol acyltransferase activation, and binding to the phospholipid transfer protein. The properties of reconstituted high density lipoprotein (HDL) particles formed from the proteins and their ability to promote cholesterol and phospholipid efflux from human skin fibroblasts were also similar. However, their ability to bind to plasma HDL subfractions differed, because twice as much proapoA-I associated with preß1-HDL and preß2-HDL subfractions compared with both mature recombinant and plasma apoA-I. Correspondingly, the amount of proapoA-I in {alpha}-HDL subfractions, especially in {alpha}1-HDL and {alpha}2-HDL, was decreased.

We conclude that while the propeptide of apoA-I is required for the effective synthesis and secretion of apoA-I, cleavage of this peptide is a requisite for the effective interconversion of HDL subfractions. Sviridov, D., L. E. Pyle, M. Jauhiainen, C. Ehnholm, and N. H. Fidge. Deletion of the propeptide of apolipoprotein A-I reduces protein expression, but stimulates effective conversion of preß-high density lipoprotein to {alpha}-high density lipoprotein. J. Lipid Res. 2000. 41: 1872;–1882.

Supplementary key words: reverse cholesterol transport, atherosclerosis, cholesterol efflux


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D. Sviridov, A. Hoang, W. Huang, and J. Sasaki
Structure-function studies of apoA-I variants: site-directed mutagenesis and natural mutations
J. Lipid Res., August 1, 2002; 43(8): 1283 - 1292.
[Abstract] [Full Text] [PDF]




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