Tolloid (Drosophila)

This chapter describes the activity, specificity and structural chemistry of Drosophila tolloid. The Drosophila tolloid (tld) and tolloid-related (tlr) genes code for Tolloid and Tolloid-related enzymes of the astacin family of metalloproteases. The Tld and Tlr are highly homologous, and are encoded by contiguous genes that appear to have arisen by a gene duplication event. Both proteins are synthesized as proenzymes that are 1057 and 1465 residues long, respectively, and have predicted signal sequences at their N-termini. The difference in overall length of these two proteins resides primarily in the pro domain that is much longer for Tlr. Following the pro domain, each protein contains an astacin-like protease motif which is in turn followed by five CUB protein-protein interaction domains interspersed with two Ca-binding epidermal growth factor-like motifs. At the blastoderm stage, tld and decapentaplegic are expressed in the dorsal half of the Drosophila embryo while sog is expressed in ventral lateral cells. Phenotypic analysis of tld mutants suggests that its primary function is to help augment Dpp activity.