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Structural Basis for Toxin Inhibition in the VapXD Toxin-Antitoxin System

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Structural Basis for Toxin Inhibition in the VapXD Toxin-Antitoxin System. / Bertelsen, Marie B; Senissar, Meriem; Nielsen, Maja H; Bisiak, Francesco; Cunha, Marta V; Molinaro, Ashley L; Daines, Dayle A; Brodersen, Ditlev E.

I: Structure, Bind 29, Nr. 2, 02.2021, s. 139-150.e3.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

Bertelsen, MB, Senissar, M, Nielsen, MH, Bisiak, F, Cunha, MV, Molinaro, AL, Daines, DA & Brodersen, DE 2021, 'Structural Basis for Toxin Inhibition in the VapXD Toxin-Antitoxin System', Structure, bind 29, nr. 2, s. 139-150.e3. https://doi.org/10.1016/j.str.2020.10.002

APA

Bertelsen, M. B., Senissar, M., Nielsen, M. H., Bisiak, F., Cunha, M. V., Molinaro, A. L., Daines, D. A., & Brodersen, D. E. (2021). Structural Basis for Toxin Inhibition in the VapXD Toxin-Antitoxin System. Structure, 29(2), 139-150.e3. https://doi.org/10.1016/j.str.2020.10.002

CBE

MLA

Vancouver

Bertelsen MB, Senissar M, Nielsen MH, Bisiak F, Cunha MV, Molinaro AL o.a. Structural Basis for Toxin Inhibition in the VapXD Toxin-Antitoxin System. Structure. 2021 feb;29(2):139-150.e3. https://doi.org/10.1016/j.str.2020.10.002

Author

Bertelsen, Marie B ; Senissar, Meriem ; Nielsen, Maja H ; Bisiak, Francesco ; Cunha, Marta V ; Molinaro, Ashley L ; Daines, Dayle A ; Brodersen, Ditlev E. / Structural Basis for Toxin Inhibition in the VapXD Toxin-Antitoxin System. I: Structure. 2021 ; Bind 29, Nr. 2. s. 139-150.e3.

Bibtex

@article{0a8066decf5846fa8282419ace11ed64,
title = "Structural Basis for Toxin Inhibition in the VapXD Toxin-Antitoxin System",
abstract = "Bacterial type II toxin-antitoxin (TA) modules encode a toxic protein that downregulates metabolism and a specific antitoxin that binds and inhibits the toxin during normal growth. In non-typeable Haemophilus influenzae, a common cause of infections in humans, the vapXD locus was found to constitute a functional TA module and contribute to pathogenicity; however, the mode of action of VapD and the mechanism of inhibition by the VapX antitoxin remain unknown. Here, we report the structure of the intact H. influenzae VapXD complex, revealing an unusual 2:1 TA molecular stoichiometry where a Cas2-like homodimer of VapD binds a single VapX antitoxin. VapX consists of an oligonucleotide/oligosaccharide-binding domain that docks into an asymmetrical cavity on the toxin dimer. Structures of isolated VapD further reveal how a symmetrical toxin homodimer adapts to interacting with an asymmetrical antitoxin and suggest how a primordial TA system evolved to become part of CRISPR-Cas immunity systems.",
keywords = "CRISPR-Cas, Cas2, Haemophilus influenzae, OB fold, RNase, VapD",
author = "Bertelsen, {Marie B} and Meriem Senissar and Nielsen, {Maja H} and Francesco Bisiak and Cunha, {Marta V} and Molinaro, {Ashley L} and Daines, {Dayle A} and Brodersen, {Ditlev E}",
note = "Copyright {\textcopyright} 2020 Elsevier Ltd. All rights reserved.",
year = "2021",
month = feb,
doi = "10.1016/j.str.2020.10.002",
language = "English",
volume = "29",
pages = "139--150.e3",
journal = "Structure",
issn = "0969-2126",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - Structural Basis for Toxin Inhibition in the VapXD Toxin-Antitoxin System

AU - Bertelsen, Marie B

AU - Senissar, Meriem

AU - Nielsen, Maja H

AU - Bisiak, Francesco

AU - Cunha, Marta V

AU - Molinaro, Ashley L

AU - Daines, Dayle A

AU - Brodersen, Ditlev E

N1 - Copyright © 2020 Elsevier Ltd. All rights reserved.

PY - 2021/2

Y1 - 2021/2

N2 - Bacterial type II toxin-antitoxin (TA) modules encode a toxic protein that downregulates metabolism and a specific antitoxin that binds and inhibits the toxin during normal growth. In non-typeable Haemophilus influenzae, a common cause of infections in humans, the vapXD locus was found to constitute a functional TA module and contribute to pathogenicity; however, the mode of action of VapD and the mechanism of inhibition by the VapX antitoxin remain unknown. Here, we report the structure of the intact H. influenzae VapXD complex, revealing an unusual 2:1 TA molecular stoichiometry where a Cas2-like homodimer of VapD binds a single VapX antitoxin. VapX consists of an oligonucleotide/oligosaccharide-binding domain that docks into an asymmetrical cavity on the toxin dimer. Structures of isolated VapD further reveal how a symmetrical toxin homodimer adapts to interacting with an asymmetrical antitoxin and suggest how a primordial TA system evolved to become part of CRISPR-Cas immunity systems.

AB - Bacterial type II toxin-antitoxin (TA) modules encode a toxic protein that downregulates metabolism and a specific antitoxin that binds and inhibits the toxin during normal growth. In non-typeable Haemophilus influenzae, a common cause of infections in humans, the vapXD locus was found to constitute a functional TA module and contribute to pathogenicity; however, the mode of action of VapD and the mechanism of inhibition by the VapX antitoxin remain unknown. Here, we report the structure of the intact H. influenzae VapXD complex, revealing an unusual 2:1 TA molecular stoichiometry where a Cas2-like homodimer of VapD binds a single VapX antitoxin. VapX consists of an oligonucleotide/oligosaccharide-binding domain that docks into an asymmetrical cavity on the toxin dimer. Structures of isolated VapD further reveal how a symmetrical toxin homodimer adapts to interacting with an asymmetrical antitoxin and suggest how a primordial TA system evolved to become part of CRISPR-Cas immunity systems.

KW - CRISPR-Cas

KW - Cas2

KW - Haemophilus influenzae

KW - OB fold

KW - RNase

KW - VapD

UR - http://www.scopus.com/inward/record.url?scp=85096123215&partnerID=8YFLogxK

U2 - 10.1016/j.str.2020.10.002

DO - 10.1016/j.str.2020.10.002

M3 - Journal article

C2 - 33096014

VL - 29

SP - 139-150.e3

JO - Structure

JF - Structure

SN - 0969-2126

IS - 2

ER -