The ectodomain of HIV-1 env subunit gp41 forms a soluble, alpha-helical, rod-like oligomer in the absence of gp120 and the N-terminal fusion peptide

EMBO J. 1996 Apr 1;15(7):1507-14.


The human immunodeficiency virus-1 (HIV-1) envelope glycoprotein is composed of a soluble glycopolypeptide gp120 and a transmembrane glycopolypeptide gp41. These subunits form non-covalently linked oligomers on the surface of infected cells, virions and cells transfected with the complete env gene. Two length variants of the extracellular domain of gp41 (aa 21-166 and aa 39-166), that both lack the N-terminal fusion peptide and the C-terminal membrane anchor and cytoplasmic domain, have been expressed in insect cells to yield soluble oligomeric gp41 proteins. Oligomerization was confirmed by chemical cross-linking and gel filtration. Electron microscopy and circular dichroism measurements indicate a rod-like molecule with a high alpha-helical content and a high melting temperature (78 degrees C). The binding of monoclonal antibody Fab fragments dramatically increased the solubility of both gp41 constructs. We propose that gp41 folds into its membrane fusion-active conformation, when expressed alone.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Cell Line
  • Disulfides / chemistry
  • Genes, env
  • HIV Antibodies
  • HIV Envelope Protein gp120 / chemistry
  • HIV Envelope Protein gp41 / chemistry*
  • HIV Envelope Protein gp41 / genetics
  • HIV Envelope Protein gp41 / immunology
  • HIV-1 / chemistry*
  • HIV-1 / genetics
  • HIV-1 / immunology
  • Humans
  • Immunoglobulin Fab Fragments
  • Insecta
  • Microscopy, Electron
  • Protein Conformation
  • Protein Structure, Secondary
  • Solubility
  • Thermodynamics
  • Viral Fusion Proteins / chemistry


  • Antibodies, Monoclonal
  • Disulfides
  • HIV Antibodies
  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp41
  • Immunoglobulin Fab Fragments
  • Viral Fusion Proteins