Characterization of an Actin-targeting ADP-ribosyltransferase from Aeromonas hydrophila

Shniffer, Adin; Visschedyk, Danielle D.; Ravulapalli, R.; Suárez, Giovanni; Turgeon, Zachari; Petrie, Anthony; Chopra, Ashok K.; Merrill, A. Rod

doi:10.1074/jbc.m112.397612

Cited by 15 publications

(20 citation statements)

References 59 publications

(67 reference statements)

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“…The high-resolution structure and simple reaction mechanism reported here will provide an understanding of the reaction. Finally, the unique complex structure also provides valuable information needed to design inhibitors of ART family proteins (38).…”

Section: Discussionmentioning

confidence: 99%

Arginine ADP-ribosylation mechanism based on structural snapshots of iota-toxin and actin complex

Tsurumura

Tsumori

Qiu

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Section: Discussionmentioning

confidence: 99%

Arginine ADP-ribosylation mechanism based on structural snapshots of iota-toxin and actin complex

Tsurumura

Tsumori

Qiu

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…Another mART actin-modifying toxin with known structure is VahC from A. hydrophila [39]. Unfortunately, the N-terminal truncated structures (PDBs: 4FML and 3NTS) lack the coordinates corresponding to the T-segment (i.e., upstream α 2 ).…”

Section: Resultsmentioning

confidence: 99%

“…These proteins are related to C3-like toxins (single-domain A-component with QxE catalytic motif that ADP-ribosylate Rho proteins) but also show features of C2-like toxins (require a binding/translocation partner, B-component) for intoxication. SpvB toxin (UP: P555220) from Salmonella enterica [38], VahC toxin (UP: Q49TP5) from Aeromonas hydrophila [39], and Photox toxin (UP: Q7N9B1) from Photorhabdus luminescens [40] possess the ExE motif, ADP-ribosylate G-actin, and are two-domains toxins (C-domain has mART activity). AexU toxin (UP: A0FKE5) from A. hydrophila [41] has a domain organization like AexT and is secreted into target cells by using the type III secretion system and harbors the catalytic QxE motif rather than the ExE motif characteristic of ExoS- like toxins.…”

Section: Introductionmentioning

confidence: 99%

An In-Silico Sequence-Structure-Function Analysis of the N-Terminal Lobe in CT Group Bacterial ADP-Ribosyltransferase Toxins

Lugo

Merrill

2019

Toxins

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The C3-like toxins are single-domain proteins that represent a minimal mono-ADP-ribosyl transferase (mART) enzyme with a simple model scaffold for the entire cholera toxin (CT)-group. These proteins possess a single (A-domain) that modifies Rho proteins. In contrast, C2-like toxins require a binding/translocation partner (B-component) for intoxication. These are A-only toxins that contain the E-x-E motif, modify G-actin, but are two-domains with a C-domain possessing enzymatic activity. The N-domain of the C2-like toxins is unstructured, and its function is currently unknown. A sequence-structure-function comparison was performed on the N-terminal region of the mART domain of the enzymatic component of the CT toxin group in the CATCH fold (3.90.210.10). Special consideration was given to the N-domain distal segment, the α-lobe (α1–α4), and its different roles in these toxin sub-groups. These results show that the role of the N-terminal α-lobe is to provide a suitable configuration (i) of the α2–α3 helices to feature the α3-motif that has a role in NAD+ substrate binding and possibly in the interaction with the protein target; (ii) the α3–α4 helices to provide the α3/4-loop with protein-protein interaction capability; and (iii) the α1-Ntail that features specialized motif(s) according to the toxin type (A-only or A-B toxins) exhibiting an effect on the catalytic activity via the ARTT-loop, with a role in the inter-domain stability, and with a function in the binding and/or translocation steps during the internalization process.

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“…Interestingly, certain eukaryotic DNA viruses, such as the Paramecium bursaria Chlorella virus (PBCV1_A092/093L) also encode an ART belonging to this family, which is packaged into the virion (Dunigan et al 2012), suggesting that it might be deployed right after infection just as with the bacteriophage versions. Other members are toxins deployed by various animal pathogenic bacteria such as B. cereus VIP2, C. perfringens iota, C. botulinum C2 and C3, B. anthracis lethal factor, Aeromonas hydrophila VahC and Salmonella SpvB (Corda and Di Girolamo 2003; Fieldhouse et al 2010; Shniffer et al 2012; Ueda and Hayaishi 1985). These proteins frequently target specific host proteins such as actin and the small GTPase Rho.…”

Section: Evolutionary History and Diversity Of The Art Superfamilymentioning

confidence: 99%

The Natural History of ADP-Ribosyltransferases and the ADP-Ribosylation System

Aravind

Zhang

Souza

et al. 2014

Current Topics in Microbiology and Immunology

173

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Catalysis of NAD+-dependent ADP-ribosylation of proteins, nucleic acids, or small molecules has evolved in at least three structurally unrelated superfamilies of enzymes, namely ADP-ribosyltransferase (ART), the Sirtuins, and probably TM1506. Of these, the ART superfamily is the most diverse in terms of structure, active site residues, and targets that they modify. The primary diversification of the ART superfamily occurred in the context of diverse bacterial conflict systems, wherein ARTs play both offensive and defensive roles. These include toxin–antitoxin systems, virus-host interactions, intraspecific antagonism (polymorphic toxins), symbiont/parasite effectors/toxins, resistance to antibiotics, and repair of RNAs cleaved in conflicts. ARTs evolving in these systems have been repeatedly acquired by lateral transfer throughout eukaryotic evolution, starting from the PARP family, which was acquired prior to the last eukaryotic common ancestor. They were incorporated into eukaryotic regulatory/epigenetic control systems (e.g., PARP family and NEURL4), and also used as defensive (e.g., pierisin and CARP-1 families) or immunity-related proteins (e.g., Gig2-like ARTs). The ADP-ribosylation system also includes other domains, such as the Macro, ADP-ribosyl glycohydrolase, NADAR, and ADP-ribosyl cyclase, which appear to have initially diversified in bacterial conflict-related systems. Unlike ARTs, sirtuins appear to have a much smaller presence in conflict-related systems.

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Characterization of an Actin-targeting ADP-ribosyltransferase from Aeromonas hydrophila

Abstract: Background: VahC toxin from Aeromonas hydrophila inactivates actin by transferring ADP-ribose from NAD ϩ .

Cited by 15 publications

References 59 publications

Arginine ADP-ribosylation mechanism based on structural snapshots of iota-toxin and actin complex

Arginine ADP-ribosylation mechanism based on structural snapshots of iota-toxin and actin complex

An In-Silico Sequence-Structure-Function Analysis of the N-Terminal Lobe in CT Group Bacterial ADP-Ribosyltransferase Toxins

The Natural History of ADP-Ribosyltransferases and the ADP-Ribosylation System

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