Crystal structure of the simian immunodeficiency virus (SIV) gp41 core: conserved helical interactions underlie the broad inhibitory activity of gp41 peptides

Proc Natl Acad Sci U S A. 1998 Aug 4;95(16):9134-9. doi: 10.1073/pnas.95.16.9134.


The gp41 subunit of the envelope protein complex from human and simian immunodeficiency viruses (HIV and SIV) mediates membrane fusion during viral entry. The crystal structure of the HIV-1 gp41 ectodomain core in its proposed fusion-active state is a six-helix bundle. Here we have reconstituted the core of the SIV gp41 ectodomain with two synthetic peptides called SIV N36 and SIV C34, which form a highly helical trimer of heterodimers. The 2.2 A resolution crystal structure of this SIV N36/C34 complex is very similar to the analogous structure in HIV-1 gp41. In both structures, three N36 helices form a central trimeric coiled coil. Three C34 helices pack in an antiparallel orientation into highly conserved, hydrophobic grooves along the surface of this coiled coil. The conserved nature of the N36-C34 interface suggests that the HIV-1 and SIV peptides are functionally interchangeable. Indeed, a heterotypic complex between HIV-1 N36 and SIV C34 peptides is highly helical and stable. Moreover, as with HIV-1 C34, the SIV C34 peptide is a potent inhibitor of HIV-1 infection. These results identify conserved packing interactions between the N and C helices of gp41 and have implications for the development of C peptide analogs with broad inhibitory activity.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Circular Dichroism
  • HIV Envelope Protein gp41 / chemistry
  • HIV-1 / chemistry
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / metabolism
  • Molecular Sequence Data
  • Peptide Fragments / metabolism*
  • Protein Conformation
  • Retroviridae Proteins / chemistry*
  • Retroviridae Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Simian Immunodeficiency Virus / chemistry*
  • Solutions
  • Viral Envelope Proteins / chemistry*


  • HIV Envelope Protein gp41
  • Membrane Glycoproteins
  • Peptide Fragments
  • Retroviridae Proteins
  • SIV envelope protein gp41
  • Solutions
  • Viral Envelope Proteins

Associated data

  • PDB/2 SIV