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Structural and functional analysis of the Klebsiella pneumoniae MazEF toxin–antitoxin system
- Source :
- IUCrJ, Vol 8, Iss 3, Pp 362-371 (2021)
- Publication Year :
- 2021
- Publisher :
- International Union of Crystallography, 2021.
-
Abstract
- Bacterial toxin–antitoxin (TA) systems correlate strongly with physiological processes in bacteria, such as growth arrest, survival and apoptosis. Here, the first crystal structure of a type II TA complex structure of Klebsiella pneumoniae at 2.3 Å resolution is presented. The K. pneumoniae MazEF complex consists of two MazEs and four MazFs in a heterohexameric assembly. It was estimated that MazEF forms a dodecamer with two heterohexameric MazEF complexes in solution, and a truncated complex exists in heterohexameric form. The MazE antitoxin interacts with the MazF toxin via two binding modes, namely, hydrophobic and hydrophilic interactions. Compared with structural homologs, K. pneumoniae MazF shows distinct features in loops β1–β2, β3–β4 and β4–β5. It can be inferred that these three loops have the potential to represent the unique characteristics of MazF, especially various substrate recognition sites. In addition, K. pneumoniae MazF shows ribonuclease activity and the catalytic core of MazF lies in an RNA-binding pocket. Mutation experiments and cell-growth assays confirm Arg28 and Thr51 as critical residues for MazF ribonuclease activity. The findings shown here may contribute to the understanding of the bacterial MazEF TA system and the exploration of antimicrobial candidates to treat drug-resistant K. pneumoniae.
- Subjects :
- mazef
Klebsiella pneumoniae
medicine.disease_cause
Biochemistry
03 medical and health sciences
medicine
General Materials Science
Ribonuclease
030304 developmental biology
Genetics
0303 health sciences
Mutation
Crystallography
biology
Chemistry
Toxin
030302 biochemistry & molecular biology
ribonuclease activity
toxin–antitoxin systems
General Chemistry
structural homologs
Condensed Matter Physics
biology.organism_classification
Toxin-antitoxin system
klebsiella pneumoniae
Dodecameric protein
QD901-999
biology.protein
Antitoxin
Bacteria
Subjects
Details
- Language :
- English
- ISSN :
- 20522525
- Volume :
- 8
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- IUCrJ
- Accession number :
- edsair.doi.dedup.....0004e4fcacab3025357d1e4f5ca58639