THE DISCOIDIN DOMAIN FAMILY REVISITED - NEW MEMBERS FROM PROKARYOTES AND A HOMOLOGY-BASED FOLD PREDICTION

Members of the discoidin (DS) domain family, which includes the C1 and C2 repeats of blood coagulation factors V and VIII, occur in a great variety of eukaryotic proteins, most of which have been implicated in cell-adhesion or developmental processes. So far, no three-dimensional structure of a known example of this extracellular module has been de termined, limiting the usefulness of identifying a new sequence as mem ber of this family. Here, we present results of a recent search of the protein sequence database for new DS domains using generalized profil es, a sensitive multiple alignment-based search technique. Several pre viously unrecognized DS domains could be identified by this method, in cluding the first examples from prokaryotic species. More importantly, we present statistical, structural, and functional evidence that the D1 domain of galactose oxidase whose three-dimensional structure has b een determined at 1.7 Angstrom resolution, is a distant member of this family. Taken together, these findings significantly expand the conce pt of the DS domain, by extending its taxonomic range and by implying a fold prediction for all its members. The proposed alignment with the galactose oxidase sequence makes it possible to construct homology-ba sed three-dimensional models for the most interesting examples, as ill ustrated by an accompanying paper on the C1 and C2 domains of factor V .