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PROSITE documentation PDOC51996

Toxin-related mono-ADP-ribosyltransferase (TR mART) core domain profile





Description

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 <PDOC51059>). 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 <PS01291>). 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 α/β-fold with a characteristic β-sandwich structure. Each domain core is formed mainly by perpendicular packing of a five-stranded mixed β-sheet against a three-stranded antiparallel β-sheet. The three-stranded sheet is flanked by four consecutive α-helices and the five-stranded sheet by an additional α-helix. A central cleft, which is formed between the four consecutive α-helices and the five-stranded β-sheet and lined by an α-helix and four β-strands, forms the NAD binding pocket (see <PDB:1QS1>). 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 β-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.

Last update:

April 2022 / First entry.

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Technical section

PROSITE method (with tools and information) covered by this documentation:

TR_MART, PS51996; Toxin-related mono-ADP-ribosyltransferase (TR mART) core domain profile  (MATRIX)


References

1AuthorsHan S. Arvai A.S. Clancy S.B. Tainer J.A.
TitleCrystal structure and novel recognition motif of rho ADP-ribosylating C3 exoenzyme from Clostridium botulinum: structural insights for recognition specificity and catalysis.
SourceJ. Mol. Biol. 305:95-107(2001).
PubMed ID11114250
DOI10.1006/jmbi.2000.4292

2AuthorsSchleberger C. Hochmann H. Barth H. Aktories K. Schulz G.E.
TitleStructure and action of the binary C2 toxin from Clostridium botulinum.
SourceJ. Mol. Biol. 364:705-715(2006).
PubMed ID17027031
DOI10.1016/j.jmb.2006.09.002

3AuthorsTsuge H. Nagahama M. Nishimura H. Hisatsune J. Sakaguchi Y. Itogawa Y. Katunuma N. Sakurai J.
TitleCrystal structure and site-directed mutagenesis of enzymatic components from Clostridium perfringens iota-toxin.
SourceJ. Mol. Biol. 325:471-483(2003).
PubMed ID12498797
DOI10.1016/s0022-2836(02)01247-0

4AuthorsHan S. Craig J.A. Putnam C.D. Carozzi N.B. Tainer J.A.
TitleEvolution and mechanism from structures of an ADP-ribosylating toxin and NAD complex.
SourceNat. Struct. Biol. 6:932-936(1999).
PubMed ID10504727
DOI10.1038/13300

5AuthorsVisschedyk D. Rochon A. Tempel W. Dimov S. Park H.-W. Merrill A.R.
TitleCerthrax toxin, an anthrax-related ADP-ribosyltransferase from Bacillus cereus.
SourceJ. Biol. Chem. 287:41089-41102(2012).
PubMed ID22992735
DOI10.1074/jbc.M112.412809

6AuthorsRavulapalli R. Lugo M.R. Pfoh R. Visschedyk D. Poole A. Fieldhouse R.J. Pai E.F. Merrill A.R.
TitleCharacterization of Vis Toxin, a Novel ADP-Ribosyltransferase from Vibrio splendidus.
SourceBiochemistry 54:5920-5936(2015).
PubMed ID26352925
DOI10.1021/acs.biochem.5b00921

7AuthorsJeong 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.
TitleStructure function analysis of an ADP-ribosyltransferase type III effector and its RNA-binding target in plant immunity.
SourceJ. Biol. Chem. 286:43272-43281(2011).
PubMed ID22013065
DOI10.1074/jbc.M111.290122

8AuthorsLiu J.-H. Yang J.-Y. Hsu D.-W. Lai Y.-H. Li Y.-P. Tsai Y.-R. Hou M.-H.
TitleCrystal Structure-Based Exploration of Arginine-Containing Peptide Binding in the ADP-Ribosyltransferase Domain of the Type III Effector XopAI Protein.
SourceInt. J. Mol. Sci. 20:0-0(2019).
PubMed ID31615004
DOI10.3390/ijms20205085

9AuthorsGlowacki G. Braren R. Firner K. Nissen M. Kuehl M. Reche P. Bazan F. Cetkovic-Cvrlje M. Leiter E. Haag F. Koch-Nolte F.
TitleThe family of toxin-related ecto-ADP-ribosyltransferases in humans and the mouse.
SourceProtein. Sci. 11:1657-1670(2002).
PubMed ID12070318
DOI10.1110/ps.0200602



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