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 pH 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 oligomeric rearrangement, the effect of low-pH treatment on the oligomeric state of different isolated forms of protein E was investigated. Full-length E dimers obtained by solubilization of virus with the detergent Triton X-100 formed trimers at low pH, whereas truncated E dimers lacking 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 reversible dissociation of the E dimers followed by an irreversible formation of trimers, a process which requires the stem-anchor portion of the protein. This region contains potential amphipathic alpha-helical and conserved structural elements whose interactions may contribute to the rearrangements which initiate the fusion process.
Institute of Virology, University of Vienna, Austria.
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K
Stiasny
S L
SL
Allison
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A
Marchler-Bauer
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C
Kunz
F X
FX
Heinz
D000595:Amino Acid Sequence; D000818:Animals; D004669:Encephalitis Viruses, Tick-Borne / Q000378:metabolism*; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014759:Viral Envelope Proteins / Q000737:chemistry*
D014759:Viral Envelope Proteins; C065696:glycoprotein E, Flavivirus