TCDB is operated by the Saier Lab Bioinformatics Group

1.G.12 The Avian Leukosis Virus gp95 Fusion Protein (ALV-gp95) Family

Retroviruses rely on low pH to activate their fusion proteins that merge the viral envelope with an endosomal membrane, releasing the viral nucleocapsid into the cytosol (Jha et al., 2011). The fusion process involves a relatively stable hemifusion-like intermediate that precedes fusion pore opening. EnvA (gp95) mediates entry through alternative receptor isoforms and intermediates of virus-endosome fusion (Jha et al., 2011). 

The long-hydrophobic viral fusion peptide (VFP) sequences are structurally constrained to access three successive states after biogenesis (Apellániz et al. 2014). Firstly, the VFP sequence must achieve a set of native interactions required for (meta) stable folding within the globular ectodomains of the glycoprotein complexes. Secondly, at the onset of the fusion process, these complexes get transferred into the target cell membrane and adopt specific conformations therein. According to commonly accepted mechanistic models, membrane-bound states of the VFP might promote the lipid bilayer remodeling required for virus-cell membrane merger. Finally, at least in some instances, several VFPs co-assemble with transmembrane anchors into membrane integral helical bundles, following a locking movement hypothetically coupled to fusion-pore expansion. Apellániz et al. 2014 reviewed different aspects of the three major states of the VFPs, including the functional assistance by other membrane-transferring glycoprotein regions. 

References associated with 1.G.12 family:

Apellániz, B., N. Huarte, E. Largo, and J.L. Nieva. (2014). The three lives of viral fusion peptides. Chem Phys Lipids 181: 40-55. 24704587
He, J., L.I. Melnik, A. Komin, G. Wiedman, T. Fuselier, C.F. Morris, C.G. Starr, P.C. Searson, W.R. Gallaher, K. Hristova, R.F. Garry, and W.C. Wimley. (2017). Ebola Virus Delta Peptide is a Viroporin. J. Virol. [Epub: Ahead of Print] 28539454
Jha, N.K., O. Latinovic, E. Martin, G. Novitskiy, M. Marin, K. Miyauchi, J. Naughton, J.A. Young, and G.B. Melikyan. (2011). Imaging single retrovirus entry through alternative receptor isoforms and intermediates of virus-endosome fusion. PLoS Pathog 7: e1001260. 21283788
Lee, J., A.J.B. Kreutzberger, L. Odongo, E.A. Nelson, D.A. Nyenhuis, V. Kiessling, B. Liang, D.S. Cafiso, J.M. White, and L.K. Tamm. (2021). Ebola virus glycoprotein interacts with cholesterol to enhance membrane fusion and cell entry. Nat Struct Mol Biol 28: 181-189. 33462517