Subdomain folding and biological activity of the core structure from human immunodeficiency virus type 1 gp41: Implications for viral membrane fusion Academic Article uri icon


MeSH Major

  • Membrane Fusion
  • Protein Conformation
  • Protein Folding


  • The envelope glycoprotein of human immunodeficiency virus type 1 (HIV-1) consists of two subunits, gp120 and gp41. The extraviral portion (ectodomain) of gp41 contains an alpha-helical domain that likely represents the core of the fusion-active conformation of the molecule. Here we report the identification and characterization of a minimal, autonomous folding subdomain that retains key determinants in specifying the overall fold of the gp41 ectodomain core. This subdomain, designated N34(L6)C28, is formed by covalent attachment of peptides N-34 and C-28 by a short flexible linker in place of the normal disulfide-bonded loop sequence. N34(L6)C28 forms a highly thermostable, alpha-helical trimer. Point mutations within the envelope protein complex that abolish membrane fusion and HIV-1 infectivity also impede the formation of the N34(L6)C28 core. Moreover, N34(L6)C28 is capable of inhibiting HIV-1 envelope-mediated membrane fusion. Taken together, these results indicate that the N34(L6)C28 core plays a direct role in the membrane fusion step of HIV-1 infection and thus provides a molecular target for the development of antiviral pharmaceutical agents.

publication date

  • May 3, 1999



  • Academic Article



  • eng

PubMed Central ID

  • PMC104224

PubMed ID

  • 10196341

Additional Document Info

start page

  • 4433

end page

  • 8


  • 73


  • 5