Abstract: Disclosed are novel compositions and methods useful for studying interactions between proteins. An N-terminal subdomain and a C-terminal subdomain of ubiquitin are linked to a pair of proteins or peptides to be examined for their ability to interact. When contacted with one another, a quasi-native ubiquitin moiety is reconstituted provided that the protein or peptide pair do, in fact, interact (bind) with one another. The quasi-native ubiquitin moiety is recognized and cleaved by ubiquitin-specific proteases after the last residue of ubiquitin. The cleavage at the quasi-native ubiquitin moiety within a linear protein fusion is the indication of interaction between the protein or peptide pair.