A Novel Protein Kinase-Like Domain in a Selenoprotein, Widespread in the Tree of Life
Open Access
- 16 February 2012
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 7 (2), e32138
- https://doi.org/10.1371/journal.pone.0032138
Abstract
Selenoproteins serve important functions in many organisms, usually providing essential oxidoreductase enzymatic activity, often for defense against toxic xenobiotic substances. Most eukaryotic genomes possess a small number of these proteins, usually not more than 20. Selenoproteins belong to various structural classes, often related to oxidoreductase function, yet a few of them are completely uncharacterised. Here, the structural and functional prediction for the uncharacterised selenoprotein O (SELO) is presented. Using bioinformatics tools, we predict that SELO protein adopts a three-dimensional fold similar to protein kinases. Furthermore, we argue that despite the lack of conservation of the “classic” catalytic aspartate residue of the archetypical His-Arg-Asp motif, SELO kinases might have retained catalytic phosphotransferase activity, albeit with an atypical active site. Lastly, the role of the selenocysteine residue is considered and the possibility of an oxidoreductase-regulated kinase function for SELO is discussed. The novel kinase prediction is discussed in the context of functional data on SELO orthologues in model organisms, FMP40 a.k.a.YPL222W (yeast), and ydiU (bacteria). Expression data from bacteria and yeast suggest a role in oxidative stress response. Analysis of genomic neighbourhoods of SELO homologues in the three domains of life points toward a role in regulation of ABC transport, in oxidative stress response, or in basic metabolism regulation. Among bacteria possessing SELO homologues, there is a significant over-representation of aquatic organisms, also of aerobic ones. The selenocysteine residue in SELO proteins occurs only in few members of this protein family, including proteins from Metazoa, and few small eukaryotes (Ostreococcus, stramenopiles). It is also demonstrated that enterobacterial mchC proteins involved in maturation of bactericidal antibiotics, microcins, form a distant subfamily of the SELO proteins. The new protein structural domain, with a putative kinase function assigned, expands the known kinome and deserves experimental determination of its biological role within the cell-signaling network.Keywords
This publication has 142 references indexed in Scilit:
- Selenoprotein P protects cells from lipid hydroperoxides generated by 15-LOX-1Prostaglandins, Leukotrienes & Essential Fatty Acids, 2010
- The Escherichia coli btuE gene, encodes a glutathione peroxidase that is induced under oxidative stress conditionsBiochemical and Biophysical Research Communications, 2010
- Defining the conserved internal architecture of a protein kinaseBiochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2010
- An enriched structural kinase database to enable kinome‐wide structure‐based analyses and drug discoveryProtein Science, 2010
- Functions and evolution of selenoprotein methionine sulfoxide reductasesBiochimica et Biophysica Acta (BBA) - General Subjects, 2009
- Protein structure prediction: when is it useful?Current Opinion in Structural Biology, 2009
- Sequence-Specific Binding to a Subset of IscR-Regulated Promoters Does Not Require IscR Fe–S Cluster LigationJournal of Molecular Biology, 2009
- Conserved herpesvirus protein kinasesBiochimica et Biophysica Acta (BBA) - Proteins and Proteomics, 2008
- Evolutionary history and higher order classification of AAA+ ATPasesJournal of Structural Biology, 2003
- Comparative Protein Modelling by Satisfaction of Spatial RestraintsJournal of Molecular Biology, 1993