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Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance

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Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance. / Rubio-Cosials, Anna; Schulz, Eike C; Lambertsen, Lotte; Smyshlyaev, Georgy; Rojas-Cordova, Carlos; Forslund, Kristoffer; Karaca, Ezgi; Bebel, Aleksandra; Bork, Peer; Barabas, Orsolya.

In: CELL, Vol. 173, No. 1, 22.03.2018, p. 208-220.e20.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Rubio-Cosials, A, Schulz, EC, Lambertsen, L, Smyshlyaev, G, Rojas-Cordova, C, Forslund, K, Karaca, E, Bebel, A, Bork, P & Barabas, O 2018, 'Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance', CELL, vol. 173, no. 1, pp. 208-220.e20. https://doi.org/10.1016/j.cell.2018.02.032

APA

Rubio-Cosials, A., Schulz, E. C., Lambertsen, L., Smyshlyaev, G., Rojas-Cordova, C., Forslund, K., Karaca, E., Bebel, A., Bork, P., & Barabas, O. (2018). Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance. CELL, 173(1), 208-220.e20. https://doi.org/10.1016/j.cell.2018.02.032

Vancouver

Rubio-Cosials A, Schulz EC, Lambertsen L, Smyshlyaev G, Rojas-Cordova C, Forslund K et al. Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance. CELL. 2018 Mar 22;173(1):208-220.e20. https://doi.org/10.1016/j.cell.2018.02.032

Bibtex

@article{285e5050bdeb45e2bf246bca2f53f5b7,
title = "Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance",
abstract = "Conjugative transposition drives the emergence of multidrug resistance in diverse bacterial pathogens, yet the mechanisms are poorly characterized. The Tn1549 conjugative transposon propagates resistance to the antibiotic vancomycin used for severe drug-resistant infections. Here, we present four high-resolution structures of the conserved Y-transposase of Tn1549 complexed with circular transposon DNA intermediates. The structures reveal individual transposition steps and explain how specific DNA distortion and cleavage mechanisms enable DNA strand exchange with an absolute minimum homology requirement. This appears to uniquely allow Tn916-like conjugative transposons to bypass DNA homology and insert into diverse genomic sites, expanding gene transfer. We further uncover a structural regulatory mechanism that prevents premature cleavage of the transposon DNA before a suitable target DNA is found and generate a peptide antagonist that interferes with the transposase-DNA structure to block transposition. Our results reveal mechanistic principles of conjugative transposition that could help control the spread of antibiotic resistance genes.",
keywords = "Amino Acid Sequence, Base Sequence, Binding Sites, Catalytic Domain, Crystallography, X-Ray, DNA Cleavage, DNA Transposable Elements/genetics, DNA, Bacterial/chemistry, Drug Resistance, Bacterial, Enterococcus faecalis/genetics, Models, Molecular, Molecular Dynamics Simulation, Mutagenesis, Site-Directed, Nucleic Acid Conformation, Protein Binding, Protein Structure, Tertiary, Recombinant Proteins/biosynthesis, Sequence Alignment, Transposases/antagonists & inhibitors",
author = "Anna Rubio-Cosials and Schulz, {Eike C} and Lotte Lambertsen and Georgy Smyshlyaev and Carlos Rojas-Cordova and Kristoffer Forslund and Ezgi Karaca and Aleksandra Bebel and Peer Bork and Orsolya Barabas",
note = "Copyright {\textcopyright} 2018 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2018",
month = mar,
day = "22",
doi = "10.1016/j.cell.2018.02.032",
language = "English",
volume = "173",
pages = "208--220.e20",
journal = "CELL",
issn = "0092-8674",
publisher = "Cell Press",
number = "1",

}

RIS

TY - JOUR

T1 - Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance

AU - Rubio-Cosials, Anna

AU - Schulz, Eike C

AU - Lambertsen, Lotte

AU - Smyshlyaev, Georgy

AU - Rojas-Cordova, Carlos

AU - Forslund, Kristoffer

AU - Karaca, Ezgi

AU - Bebel, Aleksandra

AU - Bork, Peer

AU - Barabas, Orsolya

N1 - Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2018/3/22

Y1 - 2018/3/22

N2 - Conjugative transposition drives the emergence of multidrug resistance in diverse bacterial pathogens, yet the mechanisms are poorly characterized. The Tn1549 conjugative transposon propagates resistance to the antibiotic vancomycin used for severe drug-resistant infections. Here, we present four high-resolution structures of the conserved Y-transposase of Tn1549 complexed with circular transposon DNA intermediates. The structures reveal individual transposition steps and explain how specific DNA distortion and cleavage mechanisms enable DNA strand exchange with an absolute minimum homology requirement. This appears to uniquely allow Tn916-like conjugative transposons to bypass DNA homology and insert into diverse genomic sites, expanding gene transfer. We further uncover a structural regulatory mechanism that prevents premature cleavage of the transposon DNA before a suitable target DNA is found and generate a peptide antagonist that interferes with the transposase-DNA structure to block transposition. Our results reveal mechanistic principles of conjugative transposition that could help control the spread of antibiotic resistance genes.

AB - Conjugative transposition drives the emergence of multidrug resistance in diverse bacterial pathogens, yet the mechanisms are poorly characterized. The Tn1549 conjugative transposon propagates resistance to the antibiotic vancomycin used for severe drug-resistant infections. Here, we present four high-resolution structures of the conserved Y-transposase of Tn1549 complexed with circular transposon DNA intermediates. The structures reveal individual transposition steps and explain how specific DNA distortion and cleavage mechanisms enable DNA strand exchange with an absolute minimum homology requirement. This appears to uniquely allow Tn916-like conjugative transposons to bypass DNA homology and insert into diverse genomic sites, expanding gene transfer. We further uncover a structural regulatory mechanism that prevents premature cleavage of the transposon DNA before a suitable target DNA is found and generate a peptide antagonist that interferes with the transposase-DNA structure to block transposition. Our results reveal mechanistic principles of conjugative transposition that could help control the spread of antibiotic resistance genes.

KW - Amino Acid Sequence

KW - Base Sequence

KW - Binding Sites

KW - Catalytic Domain

KW - Crystallography, X-Ray

KW - DNA Cleavage

KW - DNA Transposable Elements/genetics

KW - DNA, Bacterial/chemistry

KW - Drug Resistance, Bacterial

KW - Enterococcus faecalis/genetics

KW - Models, Molecular

KW - Molecular Dynamics Simulation

KW - Mutagenesis, Site-Directed

KW - Nucleic Acid Conformation

KW - Protein Binding

KW - Protein Structure, Tertiary

KW - Recombinant Proteins/biosynthesis

KW - Sequence Alignment

KW - Transposases/antagonists & inhibitors

U2 - 10.1016/j.cell.2018.02.032

DO - 10.1016/j.cell.2018.02.032

M3 - SCORING: Journal article

C2 - 29551265

VL - 173

SP - 208-220.e20

JO - CELL

JF - CELL

SN - 0092-8674

IS - 1

ER -