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The family of toxin-related ecto-ADP-ribosyltransferases in humans and the mouse.

Glowacki, Gustavo and Braren, Rickmer and Firner, Kathrin and Nissen, Marion and Kühl, Maren and Reche, Pedro A and Bazan, Fernando and Cetkovic-Cvrlje, Marina and Leiter, Edward and Haag, Friedrich and Koch-Nolte, Friedrich (2002) The family of toxin-related ecto-ADP-ribosyltransferases in humans and the mouse. Protein science : a publication of the Protein Society, 11 (7). pp. 1657-70. ISSN 0961-8368

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Abstract

ADP-ribosyltransferases including toxins secreted by Vibrio cholera, Pseudomonas aerurginosa, and other pathogenic bacteria inactivate the function of human target proteins by attaching ADP-ribose onto a critical amino acid residue. Cross-species polymerase chain reaction (PCR) and database mining identified the orthologs of these ADP-ribosylating toxins in humans and the mouse. The human genome contains four functional toxin-related ADP-ribosyltransferase genes (ARTs) and two related intron-containing pseudogenes; the mouse has six functional orthologs. The human and mouse ART genes map to chromosomal regions with conserved linkage synteny. The individual ART genes reveal highly restricted expression patterns, which are largely conserved in humans and the mouse. We confirmed the predicted extracellular location of the ART proteins by expressing recombinant ARTs in insect cells. Two human and four mouse ARTs contain the active site motif (R-S-EXE) typical of arginine-specific ADP-ribosyltransferases and exhibit the predicted enzyme activities. Two other human ARTs and their murine orthologues deviate in the active site motif and lack detectable enzyme activity. Conceivably, these ARTs may have acquired a new specificity or function. The position-sensitive iterative database search program PSI-BLAST connected the mammalian ARTs with most known bacterial ADP-ribosylating toxins. In contrast, no related open reading frames occur in the four completed genomes of lower eucaryotes (yeast, worm, fly, and mustard weed). Interestingly, these organisms also lack genes for ADP-ribosylhydrolases, the enzymes that reverse protein ADP-ribosylation. This suggests that the two enzyme families that catalyze reversible mono-ADP-ribosylation either were lost from the genomes of these nonchordata eucaryotes or were subject to horizontal gene transfer between kingdoms.


Item Type:Article
Uncontrolled Keywords:ADP-ribosylation; recombinant proteins; PSI-BLAST; orthologous genes; paralogous gene; cross-species PCR; ADP-Ribosylation; Recombinant proteins; PSI-BLAST; Orthologous genes; Paralogous gene; Cross-species PCR; Database searches
Subjects:Medical sciences > Biology > Evolution
Medical sciences > Biology > Molecular biology
Sciences > Computer science > Bioinformatics
ID Code:9341
Deposited On:07 Aug 2009 11:53
Last Modified:08 Oct 2009 13:52

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