| Structural highlights
Function
TACT3_SALT1 Toxic component of a type II toxin-antitoxin (TA) system (PubMed:29777131, PubMed:34556858). Acetylates tRNA and inhibits translation (PubMed:29777131). Acetylates only Gly-tRNA on all 3 Gly-tRNA(Gly) isoacceptors in situ (PubMed:35609997). In vitro acetylates mainly Ile/Leu and Gly (PubMed:29777131). Overexpression during the lag phase of a tacA3-tacT3 deletion strain leads to a 150-fold increase in persister cells in the presence of cefotaxime and a non-growth state in the absence of antibiotic (PubMed:29777131). Persister cell formation and the growth defect are neutralized by cognate antitoxin TacA3, but not by TacA1 or TacA2 (PubMed:29777131, PubMed:34556858). Plays a role in persister cell formation (PubMed:24408438).[1] [2] [3] [4] The TacA3-TacT3 complex both represses and derepresses expression of its own operon (PubMed:38538913). The hexameric 4:2 TacA3-TacT3 complex binds promoter DNA and represses its transcription; both subunits are required (PubMed:38538913). The octomeric 4:4 TacA3-TacT3 complex derepresses the operon (PubMed:38538913). The shift from hexameric to octomeric complex probably alters DNA-binding, leading to dissociation from the operator DNA and derepression (Probable) (PubMed:38538913).[5] [6]
References
- ↑ Helaine S, Cheverton AM, Watson KG, Faure LM, Matthews SA, Holden DW. Internalization of Salmonella by macrophages induces formation of nonreplicating persisters. Science. 2014 Jan 10;343(6167):204-8. PMID:24408438 doi:10.1126/science.1244705
- ↑ Rycroft JA, Gollan B, Grabe GJ, Hall A, Cheverton AM, Larrouy-Maumus G, Hare SA, Helaine S. Activity of acetyltransferase toxins involved in Salmonella persister formation during macrophage infection. Nat Commun. 2018 May 18;9(1):1993. doi: 10.1038/s41467-018-04472-6. PMID:29777131 doi:https://dx.doi.org/10.1038/s41467-018-04472-6
- ↑ Grabe GJ, Giorgio RT, Hall AMJ, Morgan RML, Dubois L, Sisley TA, Rycroft JA, Hare SA, Helaine S. Auxiliary interfaces support the evolution of specific toxin-antitoxin pairing. Nat Chem Biol. 2021 Dec;17(12):1296-1304. PMID:34556858 doi:10.1038/s41589-021-00862-y
- ↑ Bikmetov D, Hall AMJ, Livenskyi A, Gollan B, Ovchinnikov S, Gilep K, Kim JY, Larrouy-Maumus G, Zgoda V, Borukhov S, Severinov K, Helaine S, Dubiley S. GNAT toxins evolve toward narrow tRNA target specificities. Nucleic Acids Res. 2022 Jun 10;50(10):5807-5817. PMID:35609997 doi:10.1093/nar/gkac356
- ↑ Grabe GJ, Giorgio RT, Wieczór M, Gollan B, Sargen M, Orozco M, Hare SA, Helaine S. Molecular stripping underpins derepression of a toxin-antitoxin system. Nat Struct Mol Biol. 2024 Jul;31(7):1050-1060. PMID:38538913 doi:10.1038/s41594-024-01253-2
- ↑ Grabe GJ, Giorgio RT, Wieczór M, Gollan B, Sargen M, Orozco M, Hare SA, Helaine S. Molecular stripping underpins derepression of a toxin-antitoxin system. Nat Struct Mol Biol. 2024 Jul;31(7):1050-1060. PMID:38538913 doi:10.1038/s41594-024-01253-2
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