The discoidin domain family revisited: new members from prokaryotes and a homology-based fold prediction

Research output: Contribution to journalArticle

Abstract

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 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 D1 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 C1 and C2 domains of factor V.

Details

Authors
Organisations
External organisations
  • Friedrich Miescher Institute for Biomedical Research
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Developmental Biology

Keywords

  • Amino Acid Sequence, Bacterial Proteins/chemistry, Databases, Factual, Discoidins, Evolution, Molecular, Fungal Proteins/chemistry, Galactose Oxidase/chemistry, Lectins, Molecular Sequence Data, Protein Folding, Protein Structure, Tertiary, Protozoan Proteins, Sequence Alignment, Sequence Homology, Amino Acid
Original languageEnglish
Pages (from-to)1626-31
JournalProtein Science
Volume7
Issue number7
Publication statusPublished - 1998 Jul
Publication categoryResearch
Peer-reviewedYes