title: Alterations in cell membrane permeability by the lentivirus lytic peptide (LLP-1) of HIV-1 transmembrane protein.
abstract: Previously we reported that synthetic peptide homologs of an amphipathic region (designated the lentivirus lytic peptide, or LLP-1) near the carboxy terminus of HIV-1 transmembrane protein (TM) were toxic for both prokaryotic and eukaryotic cells when added exogenously to cell cultures. We postulated that these peptides may exert their toxic effects in much the same manner as natural cytolytic peptides such as magainins, cecropins, and melittin by forming pores through cellular membranes. Here we show the results of 51Cr-release assays and membrane flux measurements of peptide treated cells that support our hypothesis. We have also tested a limited panel of LLP-1 peptide analogs in these assays and found that relatively minor alterations in peptide charge or amphipathicity in the parent HIV LLP-1 sequence resulted in total loss of membrane perturbative properties. These results demonstrate that the peptide homolog of HIV-1 LLP-1 can indeed perturb membranes by forming pores of defined size in cytoplasmic membranes. Furthermore, the analog studies described here reveal that the amphipathy and high positive charge of this protein segment are required for the membrane perturbative properties.
authors.affiliation: Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pennsylvania 15261.
authors.forename: M A
authors.initials: MA
authors.lastname: Miller
authors.forename: M W
authors.initials: MW
authors.lastname: Cloyd
authors.forename: J
authors.initials: J
authors.lastname: Liebmann
authors.forename: C R
authors.initials: CR
authors.lastname: Rinaldo
authors.forename: K R
authors.initials: KR
authors.lastname: Islam
authors.forename: S Z
authors.initials: SZ
authors.lastname: Wang
authors.forename: T A
authors.initials: TA
authors.lastname: Mietzner
authors.forename: R C
authors.initials: RC
authors.lastname: Montelaro
mesh_terms: D000595:Amino Acid Sequence; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D002857:Chromium; D015700:HIV Envelope Protein gp41 / Q000633:toxicity*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: D015700:HIV Envelope Protein gp41; D002857:Chromium