Biochemical and structural studies of fragments of the ectodomain of the
human immunodeficiency virus type 1 (HIV-1) gp41 transmembrane envelope
glycoprotein have demonstrated that the molecular contacts between alpha
helices allow the formation of a trimeric coiled coil. By introducing
cysteine residues into specific locations along these alpha helices, the
normally labile HIV-1 gp160 envelope glycoprotein was converted into a
stable disulfide-linked oligomer. Although proteolytic cleavage into gp120
and gp41 glycoproteins was largely blocked, the disulfide-linked oligomer
was efficiently transported to the cell surface and was recognized by a
series of conformationally dependent antibodies. The pattern of
hetero-oligomer formation between this construct and an analogous
construct lacking portions of the gp120 variable loops and of the gp41
cytoplasmic tail demonstrates that these oligomers are trimers. These
results support the relevance of the proposed gp41 structure and
intersubunit contacts to the native, complete HIV-1 envelope glycoprotein.
Disulfide-mediated stabilization of the labile HIV-1 envelope glycoprotein
oligomer, which possesses advantages as an immunogen, will facilitate the
development of HIV-1-specific immunological reagents.
