ArticleProceedings of the National Academy of Sciences of the United States of America2008
Structural basis of actin recognition and arginine ADP-ribosylation by Clostridium perfringens iota-toxin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed, 114 citations in OpenAlex.
- Emerging Medications and Strategies in Acute Pain Management: Evolving Role of Novel Sodium and Calcium Channel Blockers, Peptide-Based Pharmacologic Drugs, and Non-Medicinal Methods.Current pain and headache reports · 2024Review
- General ADP-Ribosylation Mechanism Based on the Structure of ADP-Ribosyltransferase-Substrate Complexes.Toxins · 2024Review
- An Updated View on the Cellular Uptake and Mode-of-Action of Clostridioides difficile Toxins.Advances in experimental medicine and biology · 2024Article
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- Preclinical characterization of the efficacy and safety of biologic N-001 as a novel pain analgesic for post-operative acute pain treatment.Scientific reports · 2023Article
- Article
- Cryo-EM structures of the translocational binary toxin complex CDTa-bound CDTb-pore from Clostridioides difficile.Nature communications · 2022Article
- Structural Significance of His73 in F-Actin Dynamics: Insights from Ab Initio Study.International journal of molecular sciences · 2022Article
- Pathogenicity and virulence ofVirulence · 2021Article
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- NMR solution structures of Runella slithyformis RNA 2'-phosphotransferase Tpt1 provide insights into NAD+ binding and specificity.Nucleic acids research · 2021Article
- The Importance of Therapeutically Targeting the Binary Toxin fromInternational journal of molecular sciences · 2021Review
- Common Mechanism for Target Specificity of Protein- and DNA-Targeting ADP-Ribosyltransferases.Toxins · 2021Review
- Cryo-EM structures reveal translocational unfolding in the clostridial binary iota toxin complex.Nature structural & molecular biology · 2020Article
- Characterization of C3larvinA, a novel RhoA-targeting ADP-ribosyltransferase toxin produced by the honey bee pathogen, Paenibacillus larvae.Bioscience reports · 2020Article
- Targeting ADP-ribosylation as an antimicrobial strategy.Biochemical pharmacology · 2019Review
- ParST is a widespread toxin-antitoxin module that targets nucleotide metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Interaction ofToxins · 2018Article
- Substrate NThe Journal of biological chemistry · 2018Article
- Mechanisms of Action and Cell Death Associated withToxins · 2018Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
The ADP-ribosylating toxins (ADPRTs) produced by pathogenic bacteria modify intracellular protein and affect eukaryotic cell function. Actin-specific ADPRTs (including Clostridium perfringens iota-toxin and Clostridium botulinum C2 toxin) ADP-ribosylate G-actin at Arg-177, leading to disorganization of the cytoskeleton and cell death. Although the structures of many actin-specific ADPRTs are available, the mechanisms underlying actin recognition and selective ADP-ribosylation of Arg-177 remain unknown. Here we report the crystal structure of actin-Ia in complex with the nonhydrolyzable NAD analog betaTAD at 2.8 A resolution. The structure indicates that Ia recognizes actin via five loops around NAD: loop I (Tyr-60-Tyr-62 in the N domain), loop II (active-site loop), loop III, loop IV (PN loop), and loop V (ADP-ribosylating turn-turn loop). We used site-directed mutagenesis to confirm that loop I on the N domain and loop II are essential for the ADP-ribosyltransferase activity. Furthermore, we revealed that Glu-378 on the EXE loop is in close proximity to Arg-177 in actin, and we proposed that the ADP-ribosylation of Arg-177 proceeds by an SN1 reaction via first an oxocarbenium ion intermediate and second a cationic intermediate by alleviating the strained conformation of the first oxocarbenium ion. Our results suggest a common reaction mechanism for ADPRTs. Moreover, the structure might be of use in rational drug design to block toxin-substrate recognition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.