ArticleProteins2014
Cytotoxicity of the Vibrio vulnificus MARTX toxin effector DUF5 is linked to the C2A subdomain.
Article in Proteins, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Expression of a RAS degrader via synthetic nanocarrier-mediated mRNA delivery reduces pancreatic tumors.bioRxiv : the preprint server for biology · 2025Article
- RAS degraders: The new frontier for RAS-driven cancers.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- TheToxins · 2023Article
- DARPins bind their cytosolic targets after having been translocated through the protective antigen pore of anthrax toxin.Scientific reports · 2023Article
- Characteristic Metabolic Changes in Skeletal Muscle Due to Vibrio vulnificus Infection in a Wound Infection Model.mSystems · 2023Article
- Actin Cross-Linking Effector Domain of theInfection and immunity · 2022Article
- RAS specific protease induces irreversible growth arrest via p27 in several KRAS mutant colorectal cancer cell lines.Scientific reports · 2021Article
- Anthrax Protective Antigen Retargeted with Single-Chain Variable Fragments Delivers Enzymes to Pancreatic Cancer Cells.Chembiochem : a European journal of chemical biology · 2020Article
- TheFrontiers in microbiology · 2020Article
- RRSP and RID Effector Domains Dominate the Virulence Impact of Vibrio vulnificus MARTX Toxin.The Journal of infectious diseases · 2019Article
- Article
- The Modes of Action of MARTX Toxin Effector Domains.Toxins · 2018Review
- Structural basis of inactivation of Ras and Rap1 small GTPases by Ras/Rap1-specific endopeptidase from the sepsis-causing pathogenThe Journal of biological chemistry · 2018Article
- The bacterial Ras/Rap1 site-specific endopeptidase RRSP cleaves Ras through an atypical mechanism to disrupt Ras-ERK signaling.Science signaling · 2018Article
- Substrate Recognition of MARTX Ras/Rap1-Specific Endopeptidase.Biochemistry · 2017Article
- The membrane localization domains of two distinct bacterial toxins form a 4-helix-bundle in solution.Protein science : a publication of the Protein Society · 2017Article
- VopE, aFrontiers in cellular and infection microbiology · 2017Article
- MARTX toxins as effector delivery platforms.Pathogens and disease · 2015Review
- The Makes Caterpillars Floppy (MCF)-Like Domain of Vibrio vulnificus Induces Mitochondrion-Mediated Apoptosis.Infection and immunity · 2015Article
- Autophagy and endosomal trafficking inhibition by Vibrio cholerae MARTX toxin phosphatidylinositol-3-phosphate-specific phospholipase A1 activity.Nature communications · 2015Article
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3 authors at 1 institution in 1 country.
Funding
Abstract
The multifunctional-autoprocessing repeats-in-toxin (MARTX) toxins are bacterial protein toxins that serve as delivery platforms for cytotoxic effector domains. The domain of unknown function in position 5 (DUF5) effector domain is present in at least six different species' MARTX toxins and as a hypothetical protein in Photorhabdus spp. Its presence increases the potency of the Vibrio vulnificus MARTX toxin in mouse virulence studies, indicating DUF5 directly contributes to pathogenesis. In this work, DUF5 is shown to be cytotoxic when transiently expressed in HeLa cells. DUF5 localized to the plasma membrane dependent upon its C1 domain and the cells become rounded dependent upon its C2 domain. Both full-length DUF5 and the C2 domain caused growth inhibition when expressed in Saccharomyces cerevisiae. A structural model of DUF5 was generated based on the structure of Pasteurella multocida toxin facilitating localization of the cytotoxic activity to a 186 amino acid subdomain termed C2A. Within this subdomain, an alanine scanning mutagenesis revealed aspartate-3721 and arginine-3841 as residues critical for cytotoxicity. These residues were also essential for HeLa cell intoxication when purified DUF5 fused to anthrax toxin lethal factor was delivered cytosolically. Thermal shift experiments indicated that these conserved residues are important to maintain protein structure, rather than for catalysis. The Aeromonas hydrophila MARTX toxin DUF5(Ah) domain was also cytotoxic, while the weakly conserved C1-C2 domains from P. multocida toxin were not. Overall, this study is the first demonstration that DUF5 as found in MARTX toxins has cytotoxic activity that depends on conserved residues in the C2A subdomain.
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