ArticleThe Journal of biological chemistry2016
Structural Analysis and Inhibition of TraE from the pKM101 Type IV Secretion System.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 43 citations in OpenAlex.
- Structural basis for TrbM-enhanced conjugation and interbacterial killing in the RP4 plasmid.iScience · 2026Article
- Flavomycin inhibits plasmid-mediated conjugative transfer of antibiotic resistance genes by disrupting energy metabolism and pilus assembly.Zoological research · 2025Article
- Inner membrane components of the plasmid pKM101 type IV secretion system TraE and TraD are DNA-binding proteins.Scientific reports · 2025Article
- Non-antibiotic compounds associated with humans and the environment can promote horizontal transfer of antimicrobial resistance genes.Critical reviews in microbiology · 2024Review
- Surface Plasmon Resonance: A Sensitive Tool to Study Protein-Protein Interactions.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Comparative Analysis of T4SS Molecular Architectures.Journal of microbiology and biotechnology · 2023Review
- Type IV secretion systems: Advances in structure, function, and activation.Molecular microbiology · 2021Review
- Possible drugs for the treatment of bacterial infections in the future: anti-virulence drugs.The Journal of antibiotics · 2021Review
- Structural and Biochemical Analysis of OrfG: The VirB8-like Component of the Conjugative Type IV Secretion System of ICEFrontiers in molecular biosciences · 2021Article
- Protein interactions within and between two F-type type IV secretion systems.Molecular microbiology · 2020Article
- Protein Dynamics in F-like Bacterial Conjugation.Biomedicines · 2020Review
- Correlation between Exogenous Compounds and the Horizontal Transfer of Plasmid-Borne Antibiotic Resistance Genes.Microorganisms · 2020Review
- Type IV Coupling Proteins as Potential Targets to Control the Dissemination of Antibiotic Resistance.Frontiers in molecular biosciences · 2020Review
- Inhibiting bacterial secretion systems in the fight against antibiotic resistance.MedChemComm · 2019Review
- Fragment-based screening identifies inhibitors of ATPase activity and of hexamer formation of Cagα from the Helicobacter pylori type IV secretion system.Scientific reports · 2019Article
- Bacteria-Killing Type IV Secretion Systems.Frontiers in microbiology · 2019Review
- Strategies to combat antimicrobial resistance: anti-plasmid and plasmid curing.FEMS microbiology reviews · 2018Review
- VirB8 homolog TraE from plasmid pKM101 forms a hexameric ring structure and interacts with the VirB6 homolog TraD.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Type IV secretion in Gram-negative and Gram-positive bacteria.Molecular microbiology · 2018Review
- Fragment-based screening identifies novel targets for inhibitors of conjugative transfer of antimicrobial resistance by plasmid pKM101.Scientific reports · 2017Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gram-negative bacteria use type IV secretion systems (T4SSs) for a variety of macromolecular transport processes that include the exchange of genetic material. The pKM101 plasmid encodes a T4SS similar to the well-studied model systems from Agrobacterium tumefaciens and Brucella suis Here, we studied the structure and function of TraE, a homolog of VirB8 that is an essential component of all T4SSs. Analysis by X-ray crystallography revealed a structure that is similar to other VirB8 homologs but displayed an altered dimerization interface. The dimerization interface observed in the X-ray structure was corroborated using the bacterial two-hybrid assay, biochemical characterization of the purified protein, and in vivo complementation, demonstrating that there are different modes of dimerization among VirB8 homologs. Analysis of interactions using the bacterial two-hybrid and cross-linking assays showed that TraE and its homologs from Agrobacterium, Brucella, and Helicobacter pylori form heterodimers. They also interact with heterologous VirB10 proteins, indicating a significant degree of plasticity in the protein-protein interactions of VirB8-like proteins. To further assess common features of VirB8-like proteins, we tested a series of small molecules derived from inhibitors of Brucella VirB8 dimerization. These molecules bound to TraE in vitro, docking predicted that they bind to a structurally conserved surface groove of the protein, and some of them inhibited pKM101 plasmid transfer. VirB8-like proteins thus share functionally important sites, and these can be exploited for the design of specific inhibitors of T4SS function.
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