MODEL FOR MUTUALLY EXCLUSIVE DOMAIN FOLDING MOLECULAR SWITCH

摘要

The present invention is a model for a mutually exclusive domain folding molecular switch comprising a two-domain, bifunctional fusion protein wherein the free energy released by the folding of a first domain of the fusion protein drives an unfolding of a second domain of the fusion protein, and vice versa. The molecular structure of the fusion protein is engineered so that, at any time, the folding of the first domain necessarily unfolds the other domain, and vice versa, thereby making the folded and unfolded states of the first and second domains mutually exclusive. This is accomplished by the insertion of an exemplary insert protein into a surface loop of an exemplary target protein subject to a novel structural design criterion wherein the N-C terminal length of the exemplary insert protein is at least two-times greater than the Calpha-Calpha length of the surface loop of the exemplary target protein.