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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].
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.
PROSITE method (with tools and information) covered by this documentation:
References
1
Authors
Han S. Arvai A.S. Clancy S.B. Tainer J.A.
Title
Crystal structure and novel recognition motif of rho ADP-ribosylating C3 exoenzyme from Clostridium botulinum: structural insights for recognition specificity and catalysis.
Liu J.-H. Yang J.-Y. Hsu D.-W. Lai Y.-H. Li Y.-P. Tsai Y.-R. Hou M.-H.
Title
Crystal Structure-Based Exploration of Arginine-Containing Peptide Binding in the ADP-Ribosyltransferase Domain of the Type III Effector XopAI Protein.
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