       Document 0612
 DOCN  M9640612
 TI    Vpr protein of human immunodeficiency virus type 1 forms
       cation-selective channels in planar lipid bilayers.
 DT    9604
 AU    Piller SC; Ewart GD; Premkumar A; Cox GB; Gage PW; John Curtin School of
       Medical Research, Australian National; University, Canberra, Australia.
 SO    Proc Natl Acad Sci U S A. 1996 Jan 9;93(1):111-5. Unique Identifier :
       AIDSLINE MED/96133887
 AB    A small (96-aa) protein, virus protein R (Vpr), of human
       immunodeficiency virus type 1 contains one hydrophobic segment that
       could form a membrane-spanning helix. Recombinant Vpr, expressed in
       Escherichia coli and purified by affinity chromatography, formed ion
       channels in planar lipid bilayers when it was added to the cis chamber
       and when the trans chamber was held at a negative potential. The
       channels were more permeable to Na+ than to Cl- ions and were inhibited
       when the trans potential was made positive. Similar channel activity was
       caused by Vpr that had a truncated C terminus, but the potential
       dependence of channel activity was no longer seen. Antibody raised to a
       peptide mimicking part of the C terminus of Vpr (AbC) inhibited channel
       activity when added to the trans chamber but had no effect when added to
       the cis chamber. Antibody to the N terminus of Vpr (AbN) increased
       channel activity when added to the cis chamber but had no effect when
       added to the trans chamber. The effects of potential and antibodies on
       channel activity are consistent with a model in which the positive
       C-terminal end of dipolar Vpr is induced to traverse the bilayer
       membrane when the opposite (trans) side of the membrane is at a negative
       potential. The C terminus of Vpr would then be available for interaction
       with AbC in the trans chamber, and the N terminus would be available for
       interaction with AbN in the cis chamber. The ability of Vpr to form ion
       channels in vitro suggests that channel formation by Vpr in vivo is
       possible and may be important in the life cycle of human
       immunodeficiency virus type 1 and/or may cause changes in cells that
       contribute to AIDS-related pathologies.
 DE    Amino Acid Sequence  Base Sequence  Computer Simulation  DNA
       Primers/CHEMISTRY  Gene Products, vpr/*CHEMISTRY  HIV-1/CHEMISTRY
       Immunologic Techniques  Ion Channel Gating  Ion Channels/*CHEMISTRY
       Lipid Bilayers  Models, Molecular  Molecular Sequence Data  Recombinant
       Proteins  JOURNAL ARTICLE

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

