8GUO

Crystal structure of the nuclease domain of EsaD in complex with EsaG from Staphylococcus aureus

Summary for 8GUO

• Entry DOI: 10.2210/pdb8guo/pdb
• Descriptor: Type VII secretion system protein EsaG, Type VII secretion system protein EssD (3 entities in total)
• Functional Keywords: toxin antitoxin, toxin, toxin-antitoxin complex, toxin/antitoxin
• Biological source: Staphylococcus aureus (strain NCTC 8325 / PS 47); More
• Total number of polymer chains: 2
• Total formula weight: 38835.39

Authors

Zhang, Z.M.,Wang, Y.J. (deposition date: 2022-09-13, release date: 2022-11-09, Last modification date: 2024-04-03)

Primary citation

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, Z.M.
A toxin-deformation dependent inhibition mechanism in the T7SS toxin-antitoxin system of Gram-positive bacteria.
Nat Commun, 13:6434-6434, 2022

PubMed Abstract: Toxin 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 ββα-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.

PubMed: 36307446
DOI: 10.1038/s41467-022-34034-w

Experimental method

X-RAY DIFFRACTION (2.59395167886 Å)