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

The human immunodeficiency virus-1 (HIV-1) envelope glycoprotein is co mposed of a soluble glycopolypeptide gp120 and a transmembrane glycopo lypeptide 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, hav e been expressed in insect cells to yield soluble oligomeric gp41 prot eins. Oligomerization was confirmed by chemical cross-linking and gel filtration. Electron microscopy and circular dichroism measurements in dicate a rod-like molecule with a high alpha-helical content and a hig h melting temperature (78 degrees C). The binding of monoclonal antibo dy Fab fragments dramatically increased the solubility of both gp41 co nstructs, We propose that gp41 folds into its membrane fusion-active c onformation, when expressed alone.