beta-Galactosidase alpha-complementation. A model of protein-protein interaction.

Studies on beta-galactosidase alpha-complementation are reviewed. The isolation and structure of two beta-galactosidase fragments that form an enzymically active complex are described. One of these is a cyanogen bromide peptide from whole beta-galactosidase; the other is a dimeric protein from a lacZ deletion mutant of Escherichia coli. The mechanism most likely involves an initial binding of two cyanogen bromide peptides to the dimer, followed by formation of a tetramer, and finally a slow conformational change of the complex to a native-like enzyme. The overall reaction is essentially irreversible. A region of the polypeptide chain involved in dimer-dimer contact must be supplied by the cyanogen bromide peptide. alpha-Complemented enzyme contains overlapping sequences. Proteolytic experiments were carried out to determine the origin of the functionally important segment. The effect on alpha-complementation of amino acid substitutions at four positions in the polypeptide chain was investigated. The implications of these results for beta-galactosidase structure and for proteins in general are discussed.