The envelope protein encoded by the vaccinia virus A17L open reading frame
is essential for virion assembly. Our mutagenesis studies indicated that cy
steines 101 and 121 form an intramolecular disulfide bond and that cysteine
178 forms an intermolecular disulfide linking two A17L molecules. This arr
angement of disulfide bonds has important implications for the topology of
the A17L protein and supports a two transmembrane model in which cysteines
101 and 121 are intraluminal and cysteine 178 is cytoplasmic. The structure
of the A17L protein, however, was not dependent on these disulfide bonds,
as a recombinant vaccinia virus with all three cysteine codons mutated to s
erines retained infectivity.