A widespread peroxiredoxin-like domain present in tumor suppression- and progression-implicated proteins.
BACKGROUND
Peroxide turnover and signalling are involved in many biological phenomena relevant to human diseases. Yet, all the players and mechanisms involved in peroxide perception are not known. Elucidating very remote evolutionary relationships between proteins is an approach that allows the discovery of novel protein functions. Here, we start with three human proteins, SRPX, SRPX2 and CCDC80, involved in tumor suppression and progression, which possess a conserved region of similarity. Structure and function prediction allowed the definition of P-DUDES, a phylogenetically widespread, possibly ancient protein structural domain, common to vertebrates and many bacterial species.


RESULTS
We show, using bioinformatics approaches, that the P-DUDES domain, surprisingly, adopts the thioredoxin-like (Thx-like) fold. A tentative, more detailed prediction of function is made, namely, that of a 2-Cys peroxiredoxin. Incidentally, consistent overexpression of all three human P-DUDES genes in two public glioblastoma microarray gene expression datasets was discovered. This finding is discussed in the context of the tumor suppressor role that has been ascribed to P-DUDES proteins in several studies. Majority of non-redundant P-DUDES proteins are found in marine metagenome, and among the bacterial species possessing this domain a trend for a higher proportion of aquatic species is observed.


CONCLUSIONS
The new protein structural domain, now with a broad enzymatic function predicted, may become a drug target once its detailed molecular mechanism of action is understood in detail.
Pawłowski
Krzysztof
K
Institute of Biochemistry and Biophysics, PAS, Pawińskiego 5A, 02-106 Warsaw, Poland. k.pawlowski@nencki.gov.pl
Muszewska
Anna
A
Lenart
Anna
A
Szczepińska
Teresa
T
Godzik
Adam
A
Grynberg
Marcin
M
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry; D017124:Conserved Sequence / Q000235:genetics; D018450:Disease Progression; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D054464:Peroxiredoxins / Q000737:chemistry*; D010802:Phylogeny; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D025521:Tumor Suppressor Proteins / Q000737:chemistry* / Q000378:metabolism
D001426:Bacterial Proteins; D008565:Membrane Proteins; C486297:SRPX protein, human; D025521:Tumor Suppressor Proteins; D054464:Peroxiredoxins