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Published on: April 25, 2014
The PIN-domain toxin-antitoxin array in mycobacteria
Vickery L Arcus1, Paul B Rainey, Susan J Turner
1AgResearch Structural Biology Laboratory, University of Auckland, Private Bag 92-019, Auckland, New Zealand. v.arcus@auckland.ac.nz
Abstract:
PIN-domains (homologues of the pilT N-terminal domain) are small protein domains of approximately 140 amino acids. They are found in a diverse range of organisms and recent evidence from bioinformatics, biochemistry, structural biology and microbiology suggest that the majority of the prokaryotic PIN-domain proteins are the toxic components of toxin-antitoxin (TA) operons. Several microorganisms have a large cohort of these operons. For example, the genome of Mycobacterium tuberculosis encodes 48 PIN-domain proteins, of which 38 are thought to be involved in TA interactions. This large array of PIN-domain TA operons raises questions as to their evolutionary origin and contemporary functional significance. We suggest that the evolutionary origin of genes encoding mycobacterial PIN-domain TA operons is linked to the mobile gene pool, but that TA operons can become resident within the chromosome of host cells from where they might be recruited to fulfil a variety of roles associated with retardation of cell growth and persistence in stressful environments.
Insights
PIN-domains are toxic protein components of toxin-antitoxin operons in prokaryotes. These operons, abundant in Mycobacterium tuberculosis, likely originated from mobile genes and aid in cell growth retardation and persistence.
Area of Science:
- Microbiology
- Molecular Biology
- Genetics
Background:
- PIN-domains are small protein domains found in diverse organisms.
- Prokaryotic PIN-domain proteins are primarily toxic components of toxin-antitoxin (TA) operons.
- Mycobacterium tuberculosis possesses a significant number of PIN-domain encoding TA operons.
Purpose of the Study:
- To investigate the evolutionary origins of mycobacterial PIN-domain TA operons.
- To understand the contemporary functional significance of these operons.
- To explore the roles of PIN-domain TA operons in bacterial cell growth and stress response.
Main Methods:
- Bioinformatics analysis to identify and categorize PIN-domain proteins.
- Biochemical and structural biology studies to characterize protein interactions.
- Microbiological investigations to assess functional roles in vivo.
Main Results:
- The majority of prokaryotic PIN-domain proteins function within TA systems.
- Mycobacterium tuberculosis encodes 48 PIN-domain proteins, with 38 implicated in TA interactions.
- Evidence suggests a link between the mobile gene pool and the origin of these operons.
Conclusions:
- PIN-domain TA operons likely evolved from mobile genetic elements.
- These operons can integrate into host chromosomes and contribute to cell growth regulation.
- They play a role in bacterial persistence under stressful environmental conditions.
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