REOVIRUS PROTEIN SIGMA-1 - FROM CELL ATTACHMENT TO PROTEIN OLIGOMERIZATION AND FOLDING MECHANISMS

The reovirus cell attachment protein sigma 1 is a lollipop-shaped stru cture with the fibrous tail anchored to the virion, Since it interacts with the cell receptor, sigma 1 is a major determinant of reovirus in fectivity and tissue tropism. Studies on its structure-function relati onships have been facilitated by the fact that protein sigma 1 produce d in any expression system is capable of binding to cell receptors. Th e use of site-specific and deletion mutants has led to the identificat ion and characterization of its virion anchorage and receptor binding domains. Studies on the oligomeric status of sigma 1 have revealed tha t sigma 1 is a homotrimer and that two independent trimerization event s at different loci (the N- and C-terminal halves, respectively) of th e protein, are involved in its generation. This also accounts for a cl early demonstrable dominant negative effect by a mutant subunit in a w ild-type/mutant sigma 1 heterotrimer. Current efforts are focused on t he involvement of chaperones in the generation of sigma 1 and on event s that take place upon sigma 1 binding to the cell receptor. Protein s igma 1 has therefore become an excellent model system for the study of both virus attachment and protein oligomerization and folding mechani sms.