8gun | pdb_00008gun
Crystal structure of mutant H528A of EsaD from Staphylococcus aureus
Structural highlights
FunctionESSD_STAA8 Component of the type VII secretion system (Ess). Plays a role in Ess secretion during infection. Required for the efficient secretion of EsxA. Required for abscess formation and staphylococcal persistence in host tissues (By similarity). Possesses a toxic DNase activity that is modulated by EssG by forming a nuclease toxin-antitoxin pair. This nuclease toxin targets competitor bacteria (PubMed:27723728).[UniProtKB:A0A0H2XIV9][1] Publication Abstract from PubMedToxin EsaD secreted by some S. aureus strains through the type VII secretion system (T7SS) specifically kills those strains lacking the antitoxin EsaG. Here we report the structures of EsaG, the nuclease domain of EsaD and their complex, which together reveal an inhibition mechanism that relies on significant conformational change of the toxin. To inhibit EsaD, EsaG breaks the nuclease domain of EsaD protein into two independent fragments that, in turn, sandwich EsaG. The originally well-folded betabetaalpha-metal finger connecting the two fragments is stretched to become a disordered loop, leading to disruption of the catalytic site of EsaD and loss of nuclease activity. This mechanism is distinct from that of the other Type II toxin-antitoxin systems, which utilize an intrinsically disordered region on the antitoxins to cover the active site of the toxins. This study paves the way for developing therapeutic approaches targeting this antagonism. A toxin-deformation dependent inhibition mechanism in the T7SS toxin-antitoxin system of Gram-positive bacteria.,Wang Y, Zhou Y, Shi C, Liu J, Lv G, Huang H, Li S, Duan L, Zheng X, Liu Y, Zhou H, Wang Y, Li Z, Ding K, Sun P, Huang Y, Lu X, Zhang ZM Nat Commun. 2022 Oct 28;13(1):6434. doi: 10.1038/s41467-022-34034-w. PMID:36307446[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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