A hyperpromiscuous antitoxin protein domain for the neutralization of diverse toxin domains
Open accessPublished version of a preprint
Abstract
Significance: Toxin–antitoxin systems are enigmatic and diverse elements of bacterial and bacteriophage genomes. We have uncovered remarkable versatility in an antitoxin protein domain that has evolved to neutralize dozens of different toxin domains. We find that antitoxins carrying this domain—Panacea—form complexes with their cognate toxins, indicating a direct neutralization mechanism, and that Panacea can be evolved to neutralize a noncognate and nonhomologous toxin with just two amino acid substitutions. This raises the possibility that this domain could be an adaptable universal or semi-universal protein neutralizer with significant biotechnological and medical potential.
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Cites
Highly accurate protein structure prediction with AlphaFold
Jumper, J., Evans, R., Pritzel, A., Green, T., Figurnov, M., Ronneberger, O., Tunyasuvunakool, K., Bates, R., Žídek, A., Potapenko, A., et al. (2021) · Nature · doi:10.1038/s41586-021-03819-2 · Cited by 43,764 · see citing works
Agents that increase the permeability of the outer membrane
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Intestinal phages interact with bacteria and are involved in human diseases
Shuwen, H., & Kefeng, D. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2113717 · Cited by 124 · see citing works
- Authors
- Kurata, T., Saha, C. K., Buttress, J. A., Mets, T., Brodiazhenko, T., Turnbull, K. J., Awoyomi, O. F., Oliveira, S. R. A., Jimmy, S., Ernits, K., Delannoy, M., Persson, K., Tenson, T., Strahl, H., Hauryliuk, V., & Atkinson, G. C.
- Affiliations
- Lund University (SE)
- Newcastle University (GB)
- University of Tartu (EE)
- Rigshospitalet (DK)
- Umeå University (SE)
- Centre for Structural Systems Biology (DE)
- Université Nice Sophia Antipolis (FR)
- Corresponding author
- Hauryliuk, Vasili
- Atkinson, Gemma C.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2022-02-04
- Volume
- 119
- Issue
- 6
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC8832971
- OpenAlex
- W4210647992
- Cited by
- 38
- References
- 3
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 9 · 2023: 13 · 2022: 7 · 2021: 1
- FWCI
- 5.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DSpace repository (University of Tartu) (submittedVersion, cc-by-nc-sa)
- DiVA at Umeå University (Umeå University) (submittedVersion, other-oa)
- Lund University Publications (Lund University) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity) (cc-by)
- Funders
- Knut och Alice Wallenbergs Stiftelse (KAW 2020.0037)
- Vetenskapsrådet (2017-03783, 2019-01085, 2018-00956)
- Ragnar Soderbergs Stiftelse (Fellowship grant)
- Umeå Centre for Microbial Research (Gender policy program grant)
- Kempestiftelserna (SMK-1858.3, Scholarship, Fall 2020)
- Carl Tryggers Stiftelse för Vetenskaplig Forskning (CTS19:24)
- Umeå University Medical Faculty (Biotechnology grant)
- European Union from the European Regional Development Fund through the Centre of Excellence in Molecular Cell Engineering (2014-2020.4.01.15-0013)
- Estonian Research Council (PRG335)
- RCUK | Biotechnology and Biological Sciences Research Council (BB/S00257X/1)
- RCUK | Medical Research Council (MR/N013840/1)
- Molecular Infection Biology Estonia - Research Capacity Building Project (H2020-WIDESPREAD-2018-2020/GA: 857518)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
- Keywords
- toxin-antitoxin systems, toxin neutralization, protein domain evolution, bacterial genomes, phage genome, protein engineering
- MeSH terms
- Protein Domains, Toxin-Antitoxin Systems, Antitoxins, Bacterial Proteins, Bacterial Toxins, Guanosine Pentaphosphate, Operon, Gene Expression Regulation, Bacterial, Burkholderia, Prophages
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