[en] The hepatitis C virus (HCV) glycoproteins E1 and E2 should be anchored in the
viral membrane by their C-terminal domains. During synthesis, they are
translocated to the endoplasmic reticulum (ER) lumen where they remain. The 31
C-terminal residues of the E1 protein and the 29 C-terminal residues of the E2
protein are implicated in the ER retention. Moreover, the E1 and E2 C termini are
implicated in E1-E2 heterodimerization. We studied the E1 and E2 C-terminal
sequences of 25 HCV strains in silico using molecular modeling techniques. We
conclude that both C-terminal domains should adopt a similar and peculiar
configuration: one amphipathic alpha-helix followed by a pair of transmembrane
beta-strands. Several three-dimensional (3-D) models were generated. After energy
minimization, their ability to interact with membranes was studied using the
molecular hydrophobicity potentials calculation and the IMPALA procedure. The
latter simulates interactions with a membrane by a Monte Carlo minimization of
energy. These methods suggest that the beta-hairpins could anchor the
glycoproteins in the ER membrane at least transiently. Anchoring could be
stabilized by the adsorption of the nearby amphipathic alpha-helices at the
membrane surface. The 3-D models correlate with experimental results which
indicate that the E1-E2 transmembrane domains are involved in the
heterodimerization and have ER retention properties.
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