Arteriosclerosis, Thrombosis, and Vascular Biology. 1996;16:328-338
© 1996 American Heart Association, Inc.
Articles |
Only the Two End Helixes of Eight Tandem Amphipathic Helical Domains of Human Apo A-I Have Significant Lipid Affinity
Implications for HDL Assembly
From the Departments of Medicine, Biochemistry, and Molecular Genetics and the Atherosclerosis Research Unit, UAB Medical Center, Birmingham, Ala (M.N.P., V.K.M., S.O.A., S.A., G.M.A., J.P.S.), and the Department of Biochemistry, Medical College of Pennsylvania and Hahnemann University, Philadelphia (S.L-K., M.C.P.).
Abstract Human apolipoprotein A-I (apo A-I) possesses
multiple tandem repeating 22-mer amphipathic 
-helixes. Computer
analysis and studies of model synthetic peptides and
recombinant protein-lipid complexes of phospholipids have suggested
that apo A-I interacts with HDL surface lipids through cooperation
among its individual amphipathic helical domains. To delineate the
overall lipid-associating properties of apo A-I, the first step is
to understand the lipid-associating properties of individual
amphipathic helical domains. To this end, we synthesized and studied
each of the eight tandem repeating 22-mer domains of apo A-I: residues
44-65, 66-87, 99-120, 121-142, 143-164, 165-186, 187-208, and 220-241.
Among the 22-mers, only the N- and C-terminal
peptides (44-65 and 220-241) were effective in clarifying multilamellar
vesicles (MLVs) of dimyristoylphosphatidylcholine (DMPC). These two
peptides also exhibited the highest partition coefficient into
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine
liposomes, the highest exclusion pressure for penetration into an egg
yolk phosphatidylcholine monolayer, and the greatest reduction in the
enthalpy of the gel-to–liquid crystalline phase transition of
DMPC MLVs. These results suggest that the strong, lipid-associating
properties of apo A-I are localized to the N- and
C-terminal amphipathic domains. Although each of the eight
peptides studied has an amphipathic structure, models based on changes
in residual effective amino acid hydrophobicity resulting from
differing depths of helix penetration into the lipid are best able to
explain the high lipid affinity possessed by the two terminal domains.
Differential scanning calorimetry (DSC) studies showed that on a molar
basis, apo A-I is about 10 times more effective than the most effective
peptide analyzed in reducing the enthalpy of the
gel-to–liquid crystalline phase transition of DMPC MLVs.
Because previous proteolysis experiments coupled with the present
DSC results suggest that the lipid-associating domains of apo A-I
are distributed throughout the length of the 243 amino acid residues,
we propose that the terminal amphipathic helical domains are involved
in the initial binding of apo A-I to the lipid surface to form HDL
particles, followed by cooperative binding of the middle six
amphipathic helical domains, perhaps aided by salt-bridge formation
between adjacent helixes arranged in an antiparallel orientation.
Key Words: protein-lipid interactions • amphipathic helical peptides • lipid affinity • helix-helix interactions • cooperative lipid association
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|
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|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
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