An amphipathic peptide from the C-terminal region of the human immunodeficiency virus envelope glycoprotein causes pore formation in membranes.
The peptide fragment of the carboxy-terminal region of the human immunodeficiency virus (HIV) transmembrane protein (gp41) has been implicated in T-cell death. This positively charged, amphipathic helix (amino acids 828 to 848) of the envelope protein is located within virions or cytoplasm. We studied the interaction of the isolated, synthetic amphipathic helix of gp41 with planar phospholipid bilayer membranes and with Sf9 cells using voltage clamp, potentiodynamic, and single-cell recording techniques. We found that the peptide binds strongly to planar membranes, especially to the negatively charged phosphatidylserine bilayer. In the presence of micromolar concentrations of peptide sufficient to make its surface densities comparable with those of envelope glycoprotein molecules in HIV virions, an increase in bilayer conductance and a decrease in bilayer stability were observed, showing pore formation in the planar lipid bilayers. These pores were permeable to both monovalent and divalent cations, as well as to chloride. The exposure of the inner leaflet of cell membranes to even 25 nM peptide increased membrane conductance. We suggest that the carboxy-terminal fragment of the HIV type 1 envelope protein may interact with the cell membrane of infected T cells to create lipidic pores which increase membrane permeability, leading to sodium and calcium flux into cells, osmotic swelling, and T-cell necrosis or apoptosis.
Chernomordik
L
L
Laboratory of Theoretical and Physical Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Chanturiya
A N
AN
Suss-Toby
E
E
Nora
E
E
Zimmerberg
J
J
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects*; D002463:Cell Membrane Permeability; D004553:Electric Conductivity; D015700:HIV Envelope Protein gp41 / Q000494:pharmacology*; D008051:Lipid Bilayers; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*
D015700:HIV Envelope Protein gp41; D008051:Lipid Bilayers; D010446:Peptide Fragments