Document 0169
 DOCN  M9460169
 TI    Interaction of the HIV-1 fusion peptide with phospholipid vesicles:
       different structural requirements for fusion and leakage.
 DT    9404
 AU    Nieva JL; Nir S; Muga A; Goni FM; Wilschut J; Department of
       Physiological Chemistry, University of Groningen,; The Netherlands.
 SO    Biochemistry. 1994 Mar 22;33(11):3201-9. Unique Identifier : AIDSLINE
       MED/94183819
 AB    This paper presents a study on the membrane fusion activity of a
       23-residue synthetic peptide, representing the N-terminus of gp41 of the
       human immunodeficiency virus type I (HIV-1; LAV1a strain), in a model
       system involving large unilamellar vesicles (LUV) composed of the
       negatively charged 1-palmitoyl-2-oleoylphosphatidylglycerol (POPG). The
       peptide (HIVarg) induced fusion of POPG LUV as evidenced by (i) mixing
       of membrane lipids, (ii) mixing of aqueous vesicle contents, and (iii)
       an irreversible increase in vesicle size. Fusion could be induced only
       in the presence of millimolar concentrations of Ca2+ or Mg2+, needed for
       induction of vesicle aggregation; the divalent cations by themselves did
       not induce any fusion. The rate constant of the fusion reaction, as
       determined by simulation of the process according to a kinetic model,
       increased dramatically with the peptide-to-lipid molar ratio, indicating
       that the peptide was the mediator of the process. In the absence of
       divalent cations, the HIVarg peptide induced leakage of small molecules
       due to formation of pores in the membrane of single vesicles. Final
       extents and kinetics of this leakage process could be simulated
       adequately by model calculations for peptide-to-lipid ratios ranging
       from 1:25 to 1:750. Experiments, in which the order of peptide and Ca2+
       addition to the vesicles was varied, indicated that the peptide is
       likely to adopt two different structures, one in the absence of Ca2+,
       primarily supporting leakage by formation of pores in separate vesicles,
       and one in the presence of Ca2+, primarily supporting fusion. Once a
       final structure had been established, it persisted even upon addition or
       removal of Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)
 DE    Calcium/PHARMACOLOGY  Cations, Divalent  Electrochemistry  HIV Envelope
       Protein gp41/CHEMISTRY/*PHARMACOLOGY  HIV-1/*CHEMISTRY  Kinetics
       Liposomes/CHEMISTRY/*METABOLISM  Magnesium/PHARMACOLOGY  *Membrane
       Fusion/DRUG EFFECTS  Peptide Fragments/CHEMISTRY/*PHARMACOLOGY
       Phosphatidylglycerols/CHEMISTRY/METABOLISM  Protein Structure, Secondary
       Spectrophotometry, Infrared  Structure-Activity Relationship  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).