Recombinant Ribonuclease VapC5 (vapC5)
Description
Definition and Biological Context
Recombinant VapC5 refers to the purified toxin protein produced via heterologous expression systems for functional studies. It belongs to the VapBC TA family, where VapB5 antitoxin neutralizes VapC5's toxicity under normal conditions. Under stress (e.g., antibiotic exposure), VapB5 degradation releases VapC5, which cleaves RNA targets to arrest growth and rewire bacterial physiology .
Enzymatic Activity
VapC5 is a Mg²⁺-dependent endoribonuclease with sequence selectivity:
Substrate Specificity
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Primary target: Cleaves tRNA<sup>SerCGA</sup> at a single site within the anticodon loop (position 36–37) .
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Mechanism: Generates 5’-monophosphate RNA fragments, validated via 5’-P RNA-seq .
Biochemical Parameters
Biological Roles in M. tuberculosis
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Growth arrest: Induces bacteriostasis in Mtb by depleting functional tRNA<sup>SerCGA</sup>, stalling translation .
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Antibiotic resistance: Reprograms transcriptome to upregulate ribosome biogenesis and WhiB7 regulon, enhancing survival against aminoglycosides (e.g., amikacin) .
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Stress adaptation: Activated under nutrient deprivation or host immune pressure to promote persistence .
Table: Experimental Insights into Recombinant VapC5
Implications and Future Directions
Recombinant VapC5 studies highlight its potential as a therapeutic target. Inhibiting VapC5 activity could sensitize Mtb to existing antibiotics, while its ribonuclease mechanism offers insights for designing sequence-specific RNA-targeting tools . Future work should clarify its endogenous RNA targets and regulatory crosstalk within the VapBC TA network.
Product Specs
Target Background
KEGG: mtu:Rv0627
STRING: 83332.Rv0627
