PreprintCited by 34Bacterial Genetics and BiotechnologyAntibiotic Resistance in BacteriaEnzyme Structure and Function

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Metamorphism of catalytic domain controls transposition in Tn3 family transposases

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Preprint — published as 10.1038/s41467-022-33871-z · Paper page

Abstract

Transposons account for a remarkable diversity of mobile genetic elements that play the role of genome architects in all domains of life. Tn3 is a family of widespread and among first identified bacterial transposons notorious for their contribution to dissemination of antibiotic resistance. Transposition within this family is mediated by a large TnpA transposase facilitating both transposition and target immunity. The structural framework for understanding the mechanism of the TnpA transposition is however absent. Here, we describe the cryo-EM structures of TnpA from Tn4430 in apo form and paired with transposon ends. We show that TnpA has a unique architecture and exhibits a family-specific regulation mechanism involving metamorphic refolding of the RNase H-like catalytic domain. The TnpA structure, constrained by a double dimerization interface, creates a unique topology that suggests a specific role for target DNA in transpososome assembly, activation, and target immunity.

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Metadata

Authors
Shkumatov, A. V., Aryanpour, N., Oger, C. A., Goossens, G., Hallet, B. F., & Efremov, R. G.
Affiliations
  • Vrije Universiteit Brussel (BE)
  • UCLouvain (BE)
Corresponding author
  • Hallet, Bernard F.
  • Efremov, Rouslan G.
Venue
Nature Communications
Publisher
openRxiv
Published
2022-02-24
Volume
13
Issue
1
Pages
6155-6155
ISSN
2041-1723 (ISSN-L)
OpenAlex
W4306721683
Cited by
34
References
1
Citations by year
2026: 13 · 2025: 11 · 2024: 3 · 2023: 6 · 2022: 1
FWCI
3.32
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Digital Access to Libraries (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Université Catholique de Louvain
  • Netherlands Centre for Electron Nanoscopy
  • European Synchrotron Radiation Facility
  • Universiteit Leiden
  • Fonds Wetenschappelijk Onderzoek (G054617N, G0H5916N)
  • Vlaams Instituut voor Biotechnologie
  • Fonds Spéciaux de Recherche
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
  • Health Sciences › Medicine › Microbiology (medical) › Antibiotic Resistance in Bacteria
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
Keywords
Tn3 transposon, DNA strand transfer, DNA cleavage, transposon ends, dimer interface, antibiotic resistance dissemination, cryo-EM structure
MeSH terms
DNA Transposable Elements, Escherichia coli, Ribonuclease H, Transposases

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