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Cryo-EM Structure of the relaxosome, a complex essential for bacterial mating and the spread of antibiotic resistance genes
Open accessPreprint — published as 10.1038/s41467-025-60116-6 · Paper page
Abstract
Bacterial mating, or conjugation was discovered nearly 80 years ago as a process transferring genes from one bacterial cell (the donor) to another (the recipient). It requires three key multiprotein complexes in the donor cell: a DNA-processing machinery called the relaxosome, a double-membrane spanning type 4 secretion system (T4SS), and an extracellular appendage termed pilus. While the near-atomic resolution structures of the T4SS and pilus are known, that of the relaxosome is not 1–3 . Here, we describe the cryo-EM structure of the fully assembled relaxosome encoded by the paradigm F plasmid in two different states corresponding to distinct functional steps along the DNA processing reaction. By varying the structures of model DNAs we delineate conformational changes required to initiate conjugation. Mutational studies of the various protein-protein and protein-DNA interaction hubs suggest a complex highly sensitive to trigger signals, that could arise from cell-to-cell contacts with recipient cells.
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Highly accurate protein structure prediction with AlphaFold
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Metadata
- Authors
- Williams, S. M., Raffl, S., Kienesberger, S., Ilangovan, A., Zechner, E. L., & Waksman, G.
- Affiliations
- Institute of Structural and Molecular Biology (GB)
- University of Graz (AT)
- Queen Mary University of London (GB)
- Corresponding author
- Williams, Sunanda M.
- Waksman, Gabriel
- Venue
- Nature Communications
- Publisher
- openRxiv
- Published
- 2024-12-20
- Volume
- 16
- Issue
- 1
- Pages
- 4906-4906
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC12117103
- OpenAlex
- W4410782288
- Cited by
- 6
- References
- 1
- Citations by year
- 2026: 5 · 2025: 1
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nature Communications (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Wellcome Trust (202679/Z/16/Z, Z/17/Z, 217089/Z/19/Z, 217089, 202679, 206166/Z/17/Z, 098302, 206166)
- Austrian Science Fund
- Biotechnology and Biological Sciences Research Council (BB/X016900/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Keywords
- relaxosome, bacterial conjugation, F plasmid, type IV secretion system, DNA processing, protein-DNA interactions, protein-protein interaction, conformational change, cell-cell contact, cryo-EM structure
- MeSH terms
- Type IV Secretion Systems, Bacterial Proteins, Conjugation, Genetic, DNA, Bacterial, Escherichia coli, F Factor, Models, Molecular, Fimbriae, Bacterial, Cryoelectron Microscopy
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