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primary topic: Structural insights into DarT toxin neutralization by cognate DarG antitoxin: ssDNA mimicry by DarG C-terminal domain keeps the DarT toxin inhibited

Structural insights into DarT toxin neutralization by cognate DarG antitoxin: ssDNA mimicry by DarG C-terminal domain keeps the DarT toxin inhibited
type: AcademicArticle
type: Article
abstract: In the DarTG toxin-antitoxin system, the DarT toxin ADP-ribosylates single-stranded DNA (ssDNA), which stalls DNA replication and plays a crucial role in controlling bacterial growth and bacteriophage infection. This toxic activity is reversed by the N-terminal macrodomain of the cognate antitoxin DarG. DarG also binds DarT, but the role of these interactions in DarT neutralization is unknown. Here, we report that the C-terminal domain of DarG (DarG toxin-binding domain [DarGTBD]) interacts with DarT to form a 1:1 stoichiometric heterodimeric complex. We determined the 2.2 Å resolution crystal structure of the Mycobacterium tuberculosis DarT-DarGTBD complex. The comparative structural analysis reveals that DarGTBD interacts with DarT at the DarT/ssDNA interaction interface, thus sterically occluding substrate ssDNA binding and consequently inactivating toxin by direct protein-protein interactions. Our data support a unique two-layered DarT toxin neutralization mechanism of DarG, which is important in keeping the toxin molecules in check under normal growth conditions.
date: 2023-07-06
volume: 31
issue: 7
is part of: Structure (London, England : 1993)
status: peerReviewed
status: published
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository
subject: QR Microbiology

Cell Press/Science Direct
type: Organization

Structure (London, England : 1993)
type: Collection
issn: 18784186

Krishan Gopal Thakur
type: Person
given name: Krishan Gopal
family name: Thakur

Japleen Kaur
type: Person
given name: Japleen
family name: Kaur

Amar Deep
type: Person
given name: Amar
family name: Deep

Maheshwaran Velusamy
type: Person
given name: Maheshwaran
family name: Velusamy

Ramandeep Singh
type: Person
given name: Ramandeep
family name: Singh

Pushpanjali Bhardwaj
type: Person
given name: Pushpanjali
family name: Bhardwaj

Latika Singh
type: Person
given name: Latika
family name: Singh

HTML Summary of #3174 Structural insights into DarT toxin neutralization by cognate DarG antitoxin: ssDNA mimicry by DarG C-terminal domain keeps the DarT toxin inhibited
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primary topic: Structural insights into DarT toxin neutralization by cognate DarG antitoxin: ssDNA mimicry by DarG C-terminal domain keeps the DarT toxin inhibited

QR Microbiology
type: Concept