Document 0984
 DOCN  M9620984
 TI    A peptide from the heptad repeat of human immunodeficiency virus gp41
       shows both membrane binding and coiled-coil formation.
 DT    9602
 AU    Rabenstein M; Shin YK; Department of Chemistry, University of
       California, Berkeley; 94720, USA.
 SO    Biochemistry. 1995 Oct 17;34(41):13390-7. Unique Identifier : AIDSLINE
       MED/96027453
 AB    The envelope glycoprotein gp41 from human immunodeficiency virus type 1
       (HIV-1) is involved in membrane fusion and virus entry. It contains a
       functionally important leucine zipper-like heptad repeat region
       (residues 553-590). To investigate the solution structure and
       membrane-binding properties of this region, cysteine-substituted
       variants of a 38-residue peptide derived from the heptad repeat were
       synthesized and modified with nitroxide spin labels. Analytical
       equilibrium ultracentrifugation studies indicated it is primarily
       tetrameric in solution, in contrast to the protein gp160 which is a
       mixture of trimers and tetramers. Electron paramagnetic resonance (EPR)
       measurements indicated that the peptide was bound to vesicles containing
       10 mol % negatively charged lipids. The peptides were bound parallel to
       the membrane surface, near the water-membrane interface, in a structure
       different from the solution structure, most likely as monomers. When
       Asp, Pro, or Ser was substituted for Ile at the core a position of the
       heptad repeat in the middle of the peptide, the coiled coil was
       destabilized. In addition, these peptides showed reduced
       membrane-binding affinities. Thus, mutations that destabilized
       coiled-coil formation also decreased membrane-binding propensity. These
       experimental results, taken with previous evidence, suggest two
       functions for the heptad repeat of gp41 after CD4 binding: (1) to form
       an extended coiled coil; (2) to provide a hydrophobic face that binds to
       the host-cell membrane, bringing the viral and cellular membranes closer
       and facilitating fusion.
 DE    Amino Acid Sequence  Binding Sites  Circular Dichroism  Comparative
       Study  Electron Spin Resonance Spectroscopy  Human  HIV Envelope Protein
       gp41/*CHEMISTRY/*METABOLISM  HIV-1/*METABOLISM  *Leucine Zippers
       Molecular Sequence Data  Peptide Fragments/*CHEMISTRY/CHEMICAL
       SYNTHESIS/METABOLISM  Phosphatidylcholines  Phosphatidylglycerols
       Protein Binding  Spin Labels  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).