STRUCTURAL REQUIREMENTS FOR LOW-PH-INDUCED REARRANGEMENTS IN THE ENVELOPE GLYCOPROTEIN OF TICK-BORNE ENCEPHALITIS-VIRUS

The exposure of the flavivirus tick-borne encephalitis (TBE) virus to an acidic pn is necessary for virus-induced membrane fusion and leads to a quantitative and irreversible conversion of the envelope protein E dimers to trimers. To study the structural requirements for this oli gomeric rearrangement, the effect of low-pH treatment on the oligomeri c state of different isolated forms of protein E was investigated. Ful l-length E dimers obtained by solubilization of virus with the deterge nt Triton X-100 formed trimers at low pH, whereas truncated E dimers l acking the stem-anchor region underwent a reversible dissociation into monomers without forming trimers. These data suggest that the low-pH- induced rearrangement in virions is a two-step process involving a rev ersible dissociation of the E dimers followed by an irreversible forma tion of trimers, a process which requires the stem-anchor portion of t he protein. This region contains potential amphipathic alpha-helical a nd conserved structural elements w hose interactions may contribute to the rearrangements which initiate the fusion process.