7RT7

Crystal structure of the RhsP2 C-terminal toxin domain in complex with its immunity protein, RhsI2

Summary for 7RT7

• Entry DOI: 10.2210/pdb7rt7/pdb
• Descriptor: RhsP2, RhsI2, 2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL, ... (4 entities in total)
• Functional Keywords: type six secretion system, effector, immunity, adp-ribosyl transferase, rna, translation, complex, toxin-antitoxin complex, toxin/antitoxin
• Biological source: Pseudomonas aeruginosa (strain UCBPP-PA14); More
• Total number of polymer chains: 12
• Total formula weight: 201935.29

Authors

Bullen, N.P.,Prehna, G.,Whitney, J.C. (deposition date: 2021-08-12, release date: 2022-08-17, Last modification date: 2024-05-22)

Primary citation

Bullen, N.P.,Sychantha, D.,Thang, S.S.,Culviner, P.H.,Rudzite, M.,Ahmad, S.,Shah, V.S.,Filloux, A.,Prehna, G.,Whitney, J.C.
An ADP-ribosyltransferase toxin kills bacterial cells by modifying structured non-coding RNAs.
Mol.Cell, 82:3484-3498.e11, 2022

PubMed Abstract: ADP-ribosyltransferases (ARTs) were among the first identified bacterial virulence factors. Canonical ART toxins are delivered into host cells where they modify essential proteins, thereby inactivating cellular processes and promoting pathogenesis. Our understanding of ARTs has since expanded beyond protein-targeting toxins to include antibiotic inactivation and DNA damage repair. Here, we report the discovery of RhsP2 as an ART toxin delivered between competing bacteria by a type VI secretion system of Pseudomonas aeruginosa. A structure of RhsP2 reveals that it resembles protein-targeting ARTs such as diphtheria toxin. Remarkably, however, RhsP2 ADP-ribosylates 2'-hydroxyl groups of double-stranded RNA, and thus, its activity is highly promiscuous with identified cellular targets including the tRNA pool and the RNA-processing ribozyme, ribonuclease P. Consequently, cell death arises from the inhibition of translation and disruption of tRNA processing. Overall, our data demonstrate a previously undescribed mechanism of bacterial antagonism and uncover an unprecedented activity catalyzed by ART enzymes.

PubMed: 36070765
DOI: 10.1016/j.molcel.2022.08.015

Experimental method

X-RAY DIFFRACTION (2.49 Å)