Characterization of mammalian ADP-ribosylation cycles.
NAD:arginine ADP-ribosyltransferases catalyze the transfer of the ADP-ribose moiety from NAD to an arginine in an acceptor protein, whereas ADP-ribosylarginine hydrolases remove ADP-ribose, regenerating free arginine and completing an ADP-ribosylation cycle. A family of four mono-ADP-ribosyltransferases was isolated and characterized from turkey erythrocytes. Transferases from rabbit and human skeletal muscle were cloned. The muscle transferases are glycosylphosphatidylinositol-anchored proteins and highly conserved across mammalian species. The rat T cell alloantigen RT6.2 has significant amino acid sequence identity to the muscle ADP-ribosyltransferase. Mammalian cells transformed with the RT6.2 coding region cDNA expressed NAD glycohydrolase activity. Sequences of RT6.2, rabbit muscle transferase and several of the bacterial toxin ADP-ribosyltransferases contain regions of amino acid similarity which, in the bacterial toxin ADP-ribosyltransferases, form the NAD-binding and active-site domains. ADP-ribosylarginine hydrolase, initially purified from turkey erythrocytes, was cloned from rat, mouse, and human brain. Deduced amino acid sequences of the rat and mouse hydrolases were 94% identical with five conserved cysteines whereas the human hydrolase sequence was 83% identical to that of the rat, with four conserved cysteines. It is unclear how an intracellular hydrolase acts in concert with a surface ADP-ribosyltransferase.
Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
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Okazaki
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Zolkiewska
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Takada
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Moss
D036002:ADP Ribose Transferases / Q000097:blood / Q000378:metabolism*; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001120:Arginine / Q000378:metabolism; D001427:Bacterial Toxins / Q000378:metabolism; D001665:Binding Sites; D017124:Conserved Sequence; D004912:Erythrocytes / Q000201:enzymology; D006026:Glycoside Hydrolases / Q000378:metabolism; D006801:Humans; D008322:Mammals; D051379:Mice; D008969:Molecular Sequence Data; D009699:N-Glycosyl Hydrolases; D009243:NAD / Q000378:metabolism*; D009244:NAD+ Nucleosidase / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017386:Sequence Homology, Amino Acid; D014422:Turkeys
D001427:Bacterial Toxins; D009243:NAD; D000246:Adenosine Diphosphate Ribose; D001120:Arginine; D036002:ADP Ribose Transferases; D006026:Glycoside Hydrolases; D009699:N-Glycosyl Hydrolases; C046422:ADP-ribosylarginine hydrolase; D009244:NAD+ Nucleosidase