Premium
The discoidin domain family revisited: New members from prokaryotes and a homology‐based fold prediction
Author(s) -
Baumgartner Stefan,
Hofmann Kay,
Bucher Philipp,
ChiquetEhrismann Ruth
Publication year - 1998
Publication title -
protein science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.353
H-Index - 175
eISSN - 1469-896X
pISSN - 0961-8368
DOI - 10.1002/pro.5560070717
Subject(s) - homology modeling , computational biology , biology , genetics , homology (biology) , sequence homology , phylogenetic tree , protein domain , discoidin domain , protein family , protein structure , evolutionary biology , gene , peptide sequence , biochemistry , signal transduction , enzyme , receptor tyrosine kinase
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 Dl domain of galactose oxidase whose three‐dimensional structure has been determined at 1.7 Å 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.