A Trimeric Structural Domain of the HIV-1 Transmembrane Glycoprotein

Nat Struct Biol. 1995 Dec;2(12):1075-82. doi: 10.1038/nsb1295-1075.

Abstract

Infection with HIV-1 is initiated by fusion of cellular and viral membranes. The gp41 subunit of the HIV-1 envelope plays a major role in this process, but the structure of gp41 is unknown. We have identified a stable, proteinase-resistant structure comprising two peptides, N-51 and C-43, derived from a recombinant protein fragment of the gp41 ectodomain. In isolation, N-51 is predominantly aggregated and C-43 is unfolded. When mixed, however, these peptides associate to form a stable, alpha-helical, discrete trimer of heterodimers. Proteolysis experiments indicate that the relative orientation of the N-51 and C-43 helices in the complex is antiparallel. We propose that N-51 forms an interior, parallel, homotrimeric, coiled-coil core, against which three C-43 helices pack in an antiparallel fashion. We suggest that this alpha-helical, trimeric complex is the core of the fusion-competent state of the HIV-1 envelope.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cloning, Molecular
  • Endopeptidases / chemistry
  • Giant Cells / chemistry
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp120 / ultrastructure*
  • HIV-1 / chemistry*
  • HIV-1 / ultrastructure
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / ultrastructure
  • Molecular Sequence Data
  • Molecular Weight
  • Peptides / chemistry
  • Proline / chemistry
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Viral Envelope Proteins / chemistry
  • Viral Envelope Proteins / ultrastructure

Substances

  • HIV Envelope Protein gp120
  • Membrane Glycoproteins
  • Peptides
  • Recombinant Proteins
  • Viral Envelope Proteins
  • Proline
  • Endopeptidases