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primary topic: Structural and functional characterization of VapBC52 toxin-antitoxin system from Mycobacterium tuberculosis

Structural and functional characterization of VapBC52 toxin-antitoxin system from Mycobacterium tuberculosis
type: AcademicArticle
type: Article
abstract: Mycobacterium tuberculosis (Mtb) encodes a huge repertoire of toxin-antitoxin (TA) systems, many of which remain uncharacterized. Here, we report the crystal structures of the VapC52 toxin and VapBC52 TA complex at a resolution of 2.6 and 3.2 Å, respectively. We show that VapC52 adopts a unique open dimeric conformation and inhibits mycobacterial growth by cleaving tRNA at the variable or anticodon loop region. Structure reveals that VapB52 adopts a distinct structural architecture and binds VapC52 with a 1:2 stoichiometry, respectively. Interestingly, binding of ssDNA activates VapB52 peptidase domain, resulting in auto-cleavage of VapB52 N-terminal domain which is critical for VapBC complex formation and neutralization. In addition to VapB52, co-expression of several other non-cognate VapB antitoxins abrogates the growth inhibition associated with VapC52 overexpression in Mycobacterium smegmatis (Msm) suggesting crosstalk among VapBC TA systems. Further, we demonstrate that the vapBC52 locus is dispensable for in vitro growth but essential for Mtb intracellular growth in macrophages and guinea pigs. Notably, VapC52 also cleaves mycobacteriophage D29 encoded tRNAs and confers resistance to phage infection in Msm. Taken together, we show that VapBC52 adopts a unique structural architecture, plays role in pathogenesis, and is possibly involved in mycobacterial antiphage defense mechanisms.
date: 2026-06-08
volume: 54
issue: 11
status: peerReviewed
status: published
author list: authors
type: EPrint
type: ArticleEPrint
is part of: repository
has document: Structural and functional characterization of VapBC52 toxin-antitoxin system from Mycobacterium tuberculosis (HTML)
subject: QR Microbiology

Structural and functional characterization of VapBC52 toxin-antitoxin system from Mycobacterium tuberculosis (HTML)
type: Document
has file: references (5).bib
has part: references (5).bib

Oxford University Press (OUP)
type: Organization

Nucleic Acids Res.
type: Collection

Vikas Jain
type: Person
given name: Vikas
family name: Jain

Charandeep Singh
type: Person
given name: Charandeep
family name: Singh

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

Manisha Singh
type: Person
given name: Manisha
family name: Singh

Munmun Bhasin
type: Person
given name: Munmun
family name: Bhasin

Akshay V Nair
type: Person
given name: Akshay V
family name: Nair

Imran Ahmad
type: Person
given name: Imran
family name: Ahmad

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

Arun Sharma
type: Person
given name: Arun
family name: Sharma

HTML Summary of #3485 Structural and functional characterization of VapBC52 toxin-antitoxin system from Mycobacterium tuberculosis
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primary topic: Structural and functional characterization of VapBC52 toxin-antitoxin system from Mycobacterium tuberculosis

QR Microbiology
type: Concept