Theoretically determined three-dimensional structures for amphipathic segments of the HIV-1 gp41 envelope protein

AIDS Res Hum Retroviruses. 1989 Feb;5(1):7-22. doi: 10.1089/aid.1989.5.7.

Abstract

Three-dimensional computer models for two segments of the C terminus of gp41, the transmembrane AIDS envelope protein, which may form amphipathic alpha-helices, have been generated using structure prediction techniques combined with energy minimization and molecular dynamics simulations. Regions gp41(772-790) and gp41(828-848) of the HXB2 strain of HIV-1 display extraordinarily high hydrophobic moment maxima as alpha-helices and when in an antiparallel conformation exhibit charge complementarity, implying that they may bind with each other and associate with the membrane. The feasibility of this hypothesis was tested in a series of computer simulations of these peptides, extended by several residues to include additional charge pairing. Beginning with a trial structure in the form of antiparallel alpha-helices of segments 770-794 and 824-856, systematic axial rotations and displacements were used to generate alternative initial states. Molecular dynamics simulations with alpha-helical torsional restraints yielded several approximately cylindrical dimeric structures highly stabilized by numerous salt links and other hydrogen bonds. This suggests that these two regions may fold back on each other in antiparallel fashion to form a loop in the tertiary structure over residues 770-856, with the loop closed by membrane-associated amphipathic alpha-helices with charged sides facing each other. We speculate that such structures could aggregate to form channels or otherwise destabilize the membrane, thereby contributing to the cytopathic effects of the gp120-gp41 complex.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Computer Simulation*
  • HIV Antigens*
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • HIV-1*
  • Hydrogen Bonding
  • Membrane Fusion
  • Models, Molecular*
  • Molecular Sequence Data
  • Peptide Fragments
  • Protein Conformation
  • Retroviridae Proteins
  • Viral Envelope Proteins*

Substances

  • HIV Antigens
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • Peptide Fragments
  • Retroviridae Proteins
  • Viral Envelope Proteins