{PDOC51996} {PS51996; TR_MART} {BEGIN} *************************************************************************** * Toxin-related mono-ADP-ribosyltransferase (TR mART) core domain profile * *************************************************************************** ADP-ribosylation is a protein modification process that occurs widely in pathogenic mechanisms, intracellular signaling systems, DNA repair, and cell division. The reaction is catalyzed by ADP-ribosyltransferases which transfer the ADP-ribose moiety of NAD to a target protein with nicotinamide release. This stereospecific reaction is catalyzed by mono- and poly-ADP- ribosyltransferases (mARTs and pARTs). mARTs catalyze the transfer of a single ADP-ribose moiety onto a specific amino acid side chain of a target protein; pARTs (also designated poly-ADP-ribose-polymerases or PARPs), additionally can catalyze the elongation and branching of ADP-ribose units on ADP-ribosylated targets (see ). The mART subfamily includes many well-known bacterial toxins as well as a number of mammalian and avian ecto-enzymes: - Clostridium botulinum C3 exoenzyme inactivates the small GTP-binding protein family Rho by ADP-ribosylating asparagine 41, which depolymerizes the actin cytoskeleton [1]. - Clostridium botulinum C2 toxin is composed of the enzyme component C2-I, which ADP-ribosylates actin, and the binding and translocation component C2-II, responsible for the interaction with eukaryotic cell receptors and the following endocytosis [2]. - Clostridium perfringens type E Iota-toxin is an ADP-ribosylating toxin (ADPRT) that ADP-ribosylates actin, which is lethal and dermonecrotic in mammals [3]. - Salmonella typhimurium Mono(ADP-ribosyl)transferase SpvB, a virulence factor. - Bacillus cereus vegetative insecticidal protein (VIP2), an insect-targeted toxin [4]. - Bacillus cereus Certhrax Toxin, an Anthrax-related ADP-ribosyltransferase. It has two domains, one that binds protective antigen and another that has ADP-ribosyltransferase activity [5]. - Vibrio splendidus Vis toxin [6]. - Pseudomonas syringae type III effector HopU1, a mono-ADP-ribosyltransferase that is injected into plant cells by the type III protein secretion system. Inside the plant cell it suppresses immunity by modifying RNA-binding proteins including the glycine-rich RNA-binding protein GRP7 [7]. - Xanthomonas axonopodis pv. citri (Xac) XopAI, a putative type III effector. Iit has been suggested to be a pathogenicity factor for citrus canker. XopAI uses an altered mART domain to bind its own N-terminal peptide containing a conserved Arg residue [8]. - Mammalian toxin-related ecto-ADP-ribosyltransferases family [Glowacki]. Most known mARTs transfer ADP-ribose onto arginine residues (see ). Some enzymatically inactive mART domains, for example, the N-terminal domains of C2 and VIP2 toxins, have acquired a new, protein-binding function. The mART domain adopts a mixed alpha/beta-fold with a characteristic beta- sandwich structure. Each domain core is formed mainly by perpendicular packing of a five-stranded mixed beta-sheet against a three-stranded antiparallel beta-sheet. The three-stranded sheet is flanked by four consecutive alpha- helices and the five-stranded sheet by an additional alpha-helix. A central cleft, which is formed between the four consecutive alpha-helices and the five-stranded beta-sheet and lined by an alpha-helix and four beta-strands, forms the NAD binding pocket (see ). Catalytically active TR mART domains hallmark catalytic residues in the active site. Specifically, (i) a catalytic Arg preceded by an aromatic residue aids in NAD(+) binding and scaffolding of the active site, (ii) a Ser-Thr-Ser motif on a beta-strand stabilizes the NAD(+) binding site, (iii) the ADP-ribosyl-turn-turn (ARTT) loop contains a catalytic Glu responsible for the ADP-ribosyltransferase activity and a Gln/Glu two residues upstream that may participate in substrate recognition, and (iv) a “phosphate-nicotinamide” (PN) loop contributes to NAD(+) binding through hydrogen bonds with an Arg and aromatic residues. The profile we developed covers the entire TR mART core domain. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: April 2022 / First entry. [ 1] Han S., Arvai A.S., Clancy S.B., Tainer J.A. "Crystal structure and novel recognition motif of rho ADP-ribosylating C3 exoenzyme from Clostridium botulinum: structural insights for recognition specificity and catalysis." J. Mol. Biol. 305:95-107(2001). PubMed=11114250; DOI=10.1006/jmbi.2000.4292 [ 2] Schleberger C., Hochmann H., Barth H., Aktories K., Schulz G.E. "Structure and action of the binary C2 toxin from Clostridium botulinum." J. Mol. Biol. 364:705-715(2006). PubMed=17027031; DOI=10.1016/j.jmb.2006.09.002 [ 3] Tsuge H., Nagahama M., Nishimura H., Hisatsune J., Sakaguchi Y., Itogawa Y., Katunuma N., Sakurai J. "Crystal structure and site-directed mutagenesis of enzymatic components from Clostridium perfringens iota-toxin." J. Mol. Biol. 325:471-483(2003). PubMed=12498797; DOI=10.1016/s0022-2836(02)01247-0 [ 4] Han S., Craig J.A., Putnam C.D., Carozzi N.B., Tainer J.A. "Evolution and mechanism from structures of an ADP-ribosylating toxin and NAD complex." Nat. Struct. Biol. 6:932-936(1999). PubMed=10504727; DOI=10.1038/13300 [ 5] Visschedyk D., Rochon A., Tempel W., Dimov S., Park H.-W., Merrill A.R. "Certhrax toxin, an anthrax-related ADP-ribosyltransferase from Bacillus cereus." J. Biol. Chem. 287:41089-41102(2012). PubMed=22992735; DOI=10.1074/jbc.M112.412809 [ 6] Ravulapalli R., Lugo M.R., Pfoh R., Visschedyk D., Poole A., Fieldhouse R.J., Pai E.F., Merrill A.R. "Characterization of Vis Toxin, a Novel ADP-Ribosyltransferase from Vibrio splendidus." Biochemistry 54:5920-5936(2015). PubMed=26352925; DOI=10.1021/acs.biochem.5b00921 [ 7] Jeong B.-R., Lin Y., Joe A., Guo M., Korneli C., Yang H., Wang P., Yu M., Cerny R.L., Staiger D., Alfano J.R., Xu Y. "Structure function analysis of an ADP-ribosyltransferase type III effector and its RNA-binding target in plant immunity." J. Biol. Chem. 286:43272-43281(2011). PubMed=22013065; DOI=10.1074/jbc.M111.290122 [ 8] Liu J.-H., Yang J.-Y., Hsu D.-W., Lai Y.-H., Li Y.-P., Tsai Y.-R., Hou M.-H. "Crystal Structure-Based Exploration of Arginine-Containing Peptide Binding in the ADP-Ribosyltransferase Domain of the Type III Effector XopAI Protein." Int. J. Mol. Sci. 20:0-0(2019). PubMed=31615004; DOI=10.3390/ijms20205085 [ 9] Glowacki G., Braren R., Firner K., Nissen M., Kuehl M., Reche P., Bazan F., Cetkovic-Cvrlje M., Leiter E., Haag F., Koch-Nolte F. "The family of toxin-related ecto-ADP-ribosyltransferases in humans and the mouse." Protein. Sci. 11:1657-1670(2002). PubMed=12070318; DOI=10.1110/ps.0200602 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}