The structural and functional investigation of the VapBC43 complex from Mycobacterium tuberculosis

Toxin – Antitoxin systems are crucial for bacterial survival against harsh circumstances such as antibiotic treatment. The VapBC systems are the most abundant Toxin-Antitoxin systems among the Toxin – Antitoxin systems in the Mycobacterium tuberculosis. The VapBC43 system is one of them, which is re...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2022-08, Vol.616, p.19-25
Main Authors: Eun, Hyun-Jong, Lee, Jooyeon, Kang, Su-Jin, Lee, Bong-Jin
Format: Article
Language:English
Subjects:
Antitoxin system
Mycobacterium tuberculosis
Toxin
X-ray crystallography
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Summary:Toxin – Antitoxin systems are crucial for bacterial survival against harsh circumstances such as antibiotic treatment. The VapBC systems are the most abundant Toxin-Antitoxin systems among the Toxin – Antitoxin systems in the Mycobacterium tuberculosis. The VapBC43 system is one of them, which is related to the response to the vancomycin treatment. However, the structure of the VapBC43 complex remained unknown. Here, we present the crystal structure of the VapBC43 complex in which a single VapB43 molecule binds to the VapC43 dimer. The electrophoretic mobility shift assay shows that the VapB43 can bind to its promoter DNA. In addition, this structure reveals that the VapC43 contains a PIN (PilT N-terminus) domain motif which is essential for ribonuclease activity but has less conserved acidic residues than other homologs. The results of ribonuclease assays show that the VapC43 exhibits ribonuclease activity despite the lack of acidic residues which are well conserved in a PIN domain superfamily. Based on the previous finding that the VapBC43 contributes to the survival of Mycobacterium tuberculosis under vancomycin treatment, the structural information of the VapBC43 complex may enable the development of the inhibitor of VapC43 that can be used as an adjuvant for vancomycin therapy against M. tuberculosis. •Type II toxin-antitoxin pair, the VapBC43 complex from Mycobacterium tuberculosis has a heterotrimeric complex.•The VapB43 from Mycobacterium tuberculosis exhibits DNA binding activity to its promoter sequence.•The VapC43 from Mycobacterium tuberculosis has a ribonuclease activity despite the unique composition of its active site.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2022.05.061