6m6v
Crystal structure the toxin-antitoxin MntA-HepT
Structural highlights
FunctionMNTA_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 PubMedThe two-gene module HEPN/MNT is predicted to be the most abundant toxin/antitoxin (TA) system in prokaryotes. However, its physiological function and neutralization mechanism remains obscure. Here, we discovered that the MntA antitoxin (MNT-domain protein) acts as an adenylyltransferase and chemically modifies the HepT toxin (HEPN-domain protein) to block its toxicity as an RNase. Biochemical and structural studies revealed that MntA mediates the transfer of three AMPs to a tyrosine residue next to the RNase domain of HepT in Shewanella oneidensis. Furthermore, in vitro enzymatic assays showed that the three AMPs are transferred to HepT by MntA consecutively with ATP serving as the substrate, and this polyadenylylation is crucial for reducing HepT toxicity. Additionally, the GSX10DXD motif, which is conserved among MntA proteins, is the key active motif for polyadenylylating and neutralizing HepT. Thus, HepT/MntA represents a new type of TA system, and the polyadenylylation-dependent TA neutralization mechanism is prevalent in bacteria and archaea. Novel polyadenylylation-dependent neutralization mechanism of the HEPN/MNT toxin/antitoxin system.,Yao J, Zhen X, Tang K, Liu T, Xu X, Chen Z, Guo Y, Liu X, Wood TK, Ouyang S, Wang X Nucleic Acids Res. 2020 Oct 12. pii: 5921292. doi: 10.1093/nar/gkaa855. PMID:33045733[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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