| Structural highlights
Function
MNTA_SHEON Antitoxin component of a type VII toxin-antitoxin (TA) system. Upon overexpression in situ or in E.coli neutralizes the effect of cognate toxin HepT (PubMed:26112399, PubMed:29555683, PubMed:33045733). Neutralization is mostly due to tri-AMPylation of toxin by this enzyme. Successively tri-AMPylates HepT on 'Tyr-104' (PubMed:33045733). Binds its own promoter, probably repressing its expression. The TA system confers plasmid stability in E.coli (PubMed:26112399).[1] [2] [3]
Publication Abstract from PubMed
Prokaryotic toxin-antitoxin (TA) systems are composed of a toxin capable of interfering with key cellular processes and its neutralizing antidote, the antitoxin. Here, we focus on the HEPN-MNT TA system encoded in the vicinity of a subtype I-D CRISPR-Cas system in the cyanobacterium Aphanizomenon flos-aquae. We show that HEPN acts as a toxic RNase, which cleaves off 4 nt from the 3' end in a subset of tRNAs, thereby interfering with translation. Surprisingly, we find that the MNT (minimal nucleotidyltransferase) antitoxin inhibits HEPN RNase through covalent di-AMPylation (diadenylylation) of a conserved tyrosine residue, Y109, in the active site loop. Furthermore, we present crystallographic snapshots of the di-AMPylation reaction at different stages that explain the mechanism of HEPN RNase inactivation. Finally, we propose that the HEPN-MNT system functions as a cellular ATP sensor that monitors ATP homeostasis and, at low ATP levels, releases active HEPN toxin.
HEPN-MNT Toxin-Antitoxin System: The HEPN Ribonuclease Is Neutralized by OligoAMPylation.,Songailiene I, Juozapaitis J, Tamulaitiene G, Ruksenaite A, Sulcius S, Sasnauskas G, Venclovas C, Siksnys V Mol Cell. 2020 Dec 17;80(6):955-970.e7. doi: 10.1016/j.molcel.2020.11.034. Epub, 2020 Dec 7. PMID:33290744[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Yao J, Guo Y, Zeng Z, Liu X, Shi F, Wang X. Identification and characterization of a HEPN-MNT family type II toxin-antitoxin in Shewanella oneidensis. Microb Biotechnol. 2015 Nov;8(6):961-73. PMID:26112399 doi:10.1111/1751-7915.12294
- ↑ Jia X, Yao J, Gao Z, Liu G, Dong YH, Wang X, Zhang H. Structure-function analyses reveal the molecular architecture and neutralization mechanism of a bacterial HEPN-MNT toxin-antitoxin system. J Biol Chem. 2018 May 4;293(18):6812-6823. doi: 10.1074/jbc.RA118.002421. Epub, 2018 Mar 19. PMID:29555683 doi:http://dx.doi.org/10.1074/jbc.RA118.002421
- ↑ Yao J, Zhen X, Tang K, Liu T, Xu X, Chen Z, Guo Y, Liu X, Wood TK, Ouyang S, Wang X. Novel polyadenylylation-dependent neutralization mechanism of the HEPN/MNT toxin/antitoxin system. Nucleic Acids Res. 2020 Nov 4;48(19):11054-11067. PMID:33045733 doi:10.1093/nar/gkaa855
- ↑ Songailiene I, Juozapaitis J, Tamulaitiene G, Ruksenaite A, Šulčius S, Sasnauskas G, Venclovas Č, Siksnys V. HEPN-MNT Toxin-Antitoxin System: The HEPN Ribonuclease Is Neutralized by OligoAMPylation. Mol Cell. 2020 Dec 17;80(6):955-970.e7. PMID:33290744 doi:10.1016/j.molcel.2020.11.034
|
