THE REOVIRUS CELL ATTACHMENT PROTEIN POSSESSES 2 INDEPENDENTLY ACTIVE TRIMERIZATION DOMAINS - BASIS OF DOMINANT NEGATIVE EFFECTS

The reovirus cell attachment protein, sigma1, is a homotrimer with an N-terminal fibrous tail and a C-terminal globular head. By cotranslating full-length and various truncated sigma1 proteins in vitro, we show that the N- and C-terminal halves of sigma1 possess independent trimerization and folding domains. Trimerization of sigma1 is initiated at the N-terminus by the formation of a "loose," protease-sensitive, three-stranded, alpha-helical coiled coil. This serves to bring the three unfolded C-termini into close proximity to one another, facilitating their subsequent trimerization and cooperative folding. Concomitant with, but independent of, this latter process, the N-terminal fiber further matures into a more stable and protease-resistant structure. The coordinated folding of sigma1 trimers exemplifies the dominant negative effects of mutant subunits in oligomeric complexes.