Functional conversion of the homologous proteins alpha-lactalbumin and lysozyme by exon exchange.

Exons of eukaryotic genes that encode proteins frequently appear to encode structural and/or functional protein units [Gilbert, W. (1978) Nature (London) 271, 501; Blake, C.C.F. (1979) Nature (London) 277, 598]. alpha-Lactalbumin and c-type lysozyme are functionally quite different but structurally highly homologous proteins. Their gene organizations have been shown to be virtually the same and their exon structures are identical. The exon 2 region of hen lysozyme contains most of the amino acid residues that make up its catalytic cleft. In this study, we engineered a hybrid protein in which the exon 2 region of goat alpha-lactalbumin was replaced with that of hen lysozyme. This conferred catalytic activity on the alpha-lactalbumin, which is a nonenzymatic protein in its native structural form.