Membrane interactions of synthetic peptides corresponding to amphipathic helical segments of the human immunodeficiency virus type-1 envelope glycoprotein
The human and simian immunodeficiency virus envelope glycoproteins, which mediate virus-induced cell fusion, contain two putative amphipathic helical segments with large helical hydrophobic moments near their carboxyl-terminal ends. In an attempt to elucidate the biological role of these amphipathic...
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Published in | The Journal of biological chemistry Vol. 267; no. 10; pp. 7121 - 7127 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Biochemistry and Molecular Biology
05.04.1992
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Subjects | |
Online Access | Get full text |
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Summary: | The human and simian immunodeficiency virus envelope glycoproteins, which mediate virus-induced cell fusion, contain two putative
amphipathic helical segments with large helical hydrophobic moments near their carboxyl-terminal ends. In an attempt to elucidate
the biological role of these amphipathic helical segments, we have synthesized peptides corresponding to residues 768-788
and 826-854 of HIV-1/WMJ-22 gp160. Circular dichroism studies of the peptides showed that the alpha helicity of the peptides
increased with the addition of dimyristoyl phosphatidylcholine (DMPC) indicating that the peptides form lipid-associating
amphipathic helixes. The peptides solubilized turbid suspensions of DMPC vesicles, and electron microscopy of peptide-DMPC
mixtures revealed the formation of discoidal complexes, suggesting that the peptides bind to and perturb lipid bilayers. The
peptides were found to lyse lipid vesicles and caused carboxyfluorescein leakage from dye-entrapped egg phosphatidylcholine
liposomes. The peptides also lysed human erythrocytes and were found to be toxic to cell cultures. At subtoxic concentrations,
the peptides effectively inhibited the fusion of CD4+ cells infected with recombinant vaccinia virus expressing human immunodeficiency
virus (HIV)-1 envelope proteins. Based on these results, and reported studies on the mutational analysis of HIV envelope proteins,
we suggest that the amphipathic helical segments near the carboxyl terminus of HIV envelope proteins may play a role in lysis
of HIV-infected cells and also may modulate the extent of cell fusion observed during HIV infection of CD4+ cells. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/s0021-9258(19)50546-4 |