The discoidin domain family revisited: New members from prokaryotes and a homology‐based fold prediction

Abstract

Abstract:Members of the discoidin (DS) domain family, which includes the CI 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 determined, limiting the usefulness of identifying a new sequence as member of this family. Here, we present results of a recent search of the protein sequence database for new DS domains using generalized profiles, a sensitive multiple alignment-based search technique. Several previously unrecognized DS domains could be identified by this method, including the first examples from prokaryotic species. More importantly, we present statistical, structural, and functional evidence that the Dl domain of galactose oxidase whose three-dimensional structure has been determined at 1.7 A resolution, is a distant member of this family. Taken together, these findings significantly expand the concept 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-based three-dimensional models for the most interesting examples, as illustrated by an accompanying paper on the CI and C2 domains of factor V.

Sea star tenacity mediated by a protein that fragments, then aggregates

“…4A and Dataset S1). These domains are known from other studies to mediate protein-protein, protein-carbohydrate, or protein-metal interactions (22)(23)(24)(25) and could therefore provide cohesive and adhesive interactions between Sfp1 and other glycans and/or proteins present in the adhesive material and in the outermost layer of the tube foot cuticle, respectively (14,16,19). To the best of our knowledge, the only other marine adhesive proteins presenting such conserved functional domains are the mussel proteins mussel foot protein 2 (mfp-2), with 11 repeats of EGF-like domains (26,27), and proximal thread matrix protein 1 (Ptmp-1), with two von Willebrand factor type A domains (28).…”

The discoidin domain receptor 1 as a novel susceptibility gene for schizophrenia

“…15 The discoidin homology domain is also present in several membrane-bound, and secreted, proteins. 16 Among these are neuropilins and contactin-associated proteins 1 and 2, which are involved in the development of the nervous system 17,18 and the XLRS-1 gene which, when mutated, causes the human X-linked inherited disease retinoschisis. 19 Collagen is the unique DDR1 ligand identified to-date and, after binding to the receptor, it follows very slow activation kinetics.…”

Effects of pathological mutations on the stability of a conserved amino acid triad in retinoschisin

“…The mature protein (23 kDa) consists almost entirely of a highly conserved discoidin domain [4]. The domain is present in single or multiple copies in extracellular or transmembrane proteins implicated in cell adhesion, cell^cell interaction [8,9] such as the coagulation factors V (FaV) [10] and VIII (FaVIII) [11], milk fat globule, neuropilin [12] and neurexins.…”