Toxin-antitoxin (TA) systems are prevalent in bacteria and are known to regulate cellular growth in response to stress. As various functions related to TA systems have been revealed, the importance of TA systems are rapidly emerging. Here, we present the crystal structure of putative mRNA interferase BC0266 and report it as a type II toxin MazF. The MazF toxin is a ribonuclease activated upon and during stressful conditions, in which it cleaves mRNA in a sequence-specific, ribosome-independent manner. Its prolonged activity causes toxic consequences to the bacteria which, in turn, may lead to bacterial death. In this study, we conducted structural and functional investigations of MazF and present the first toxin structure in the TA system of . Specifically, MazF adopts a PemK-like fold and also has an RNA substrate-recognizing loop, which is clearly observed in the high-resolution structure. Key residues of MazF involved in the catalytic activity are also proposed, and in vitro assay together with mutational studies affirm the ribonucleic activity and the active sites essential for its cellular toxicity.
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http://dx.doi.org/10.3390/toxins12060380 | DOI Listing |
J Cell Biochem
January 2025
Mastermeditech Ltd., Seoul, Republic of Korea.
Science
December 2023
Institute of Biotechnology, Life Sciences Center, Vilnius University, Saulėtekio av. 7, LT-10257 Vilnius, Lithuania.
Prokaryotic type III CRISPR-Cas antiviral systems employ cyclic oligoadenylate (cA) signaling to activate a diverse range of auxiliary proteins that reinforce the CRISPR-Cas defense. Here we characterize a class of cA-dependent effector proteins named CRISPR-Cas-associated messenger RNA (mRNA) interferase 1 (Cami1) consisting of a CRISPR-associated Rossmann fold sensor domain fused to winged helix-turn-helix and a RelE-family mRNA interferase domain. Upon activation by cyclic tetra-adenylate (cA), Cami1 cleaves mRNA exposed at the ribosomal A-site thereby depleting mRNA and leading to cell growth arrest.
View Article and Find Full Text PDFAdv Sci (Weinh)
November 2023
College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225000, China.
Engineered vector-based in vivo protein delivery platforms have made significant progress for both prophylactic and therapeutic applications. However, the lack of effective release strategies results in foreign cargo being trapped within the vector, restricting the provision of significant performance benefits and enhanced therapeutic results compared to traditional vaccines. Herein, the development of a Salmonella mRNA interferase regulation vector (SIRV) system is reported to overcome this challenge.
View Article and Find Full Text PDFFront Microbiol
August 2022
Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX, United States.
Osteomyelitis in the feet of persons with diabetes is clinically challenging and is associated with high rates of amputation. In this study RNA-sequencing was employed to explore microbial metatranscriptomes with a view to understand the relative activity and functions of the pathogen/s responsible for diabetes foot osteomyelitis (DFO). We obtained 25 intraoperative bone specimens from persons with confirmed DFO, observing that spp.
View Article and Find Full Text PDFToxins (Basel)
June 2020
The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Gwanakgu, Seoul 08826, Korea.
Toxin-antitoxin (TA) systems are prevalent in bacteria and are known to regulate cellular growth in response to stress. As various functions related to TA systems have been revealed, the importance of TA systems are rapidly emerging. Here, we present the crystal structure of putative mRNA interferase BC0266 and report it as a type II toxin MazF.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!