We report the crystal structure of an extraviral segment of a retrovirus envelope protein, the Moloney murine leukemia virus (MoMuLV) transmembrane (TM) subunit. This segment, which comprises a region of the MoMuLVTM protein analogous to that contained within the X-ray crystal structure of low-pH converted influenza hemagglutinin, contains a trimeric coiled coil, with a hydrophobic cluster at its base and a strand that packs in an antiparallel orientation against the coiled coil. This structure gives the first high-resolution insight into the retrovirus surface and serves as a model for a wide range of viral fusion proteins; key residues in this structure are conserved among C- and D-type retroviruses and the filovirus ebola.

Retrovirus envelope domain at 1.7 angstrom resolution.

Neutralizing antibodies detect a disulfide-linked glycoprotein complex within the envelope of human cytomegalovirus

Characterization of monoclonal antibodies reactive with murine leukemia viruses: Use in analysis of strains of friend MCF and friend ecotropic murine leukemia virus

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.

https://www.embopress.org/doi/pdf/10.1002/j.1460-2075.1996.tb00494.x

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.

Previous studies have indicated that the surface (SU) and transmembrane (TM) subunits of the envelope protein (Env) of murine leukemia viruses (MuLVs) are joined by a labile disulfide bond that can be stabilized by treatment of virions with thiol-specific reagents. In the present study this observation was extended to the Envs of additional classes of MuLV, and the cysteines of SU involved in this linkage were mapped by proteolytic fragmentation analyses to the CWLC sequence present at the beginning of the C-terminal domain of SU. This sequence is highly conserved across a broad range of distantly related retroviruses and resembles the CXXC motif present at the active site of thiol-disulfide exchange enzymes. A model is proposed in which rearrangements of the SU-TM intersubunit disulfide linkage, mediated by the CWLC sequence, play roles in the assembly and function of the Env complex.

Localization of the labile disulfide bond between SU and TM of the murine leukemia virus envelope protein complex to a highly conserved CWLC motif in SU that resembles the active-site sequence of thiol-disulfide exchange enzymes.

Judy Lieman-Hurwitz

Papers

The nature of the association between the murine leukemia virus envelope proteins.