A widespread peroxiredoxin-like domain present in tumor suppression- and progression-implicated proteins
1 Institute of Biochemistry and Biophysics, PAS, Pawińskiego 5A, 02-106 Warsaw, Poland
2 Nencki Institute of Experimental Biology, PAS, Pasteura 3, 02-093 Warsaw, Poland
3 Sanford|Burnham Medical Research Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92037, USA
4 Warsaw University of Life Sciences, Nowoursynowska 166, 02-787 Warsaw, Poland
BMC Genomics 2010, 11:590 doi:10.1186/1471-2164-11-590Published: 21 October 2010
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.
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.
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.