8BTO
Helical structure of BcThsA in complex with 1''-3'gcADPR
Summary for 8BTO
| Entry DOI | 10.2210/pdb8bto/pdb |
| Related | 8BTN 8BTP |
| EMDB information | 16233 |
| Descriptor | NAD(+) hydrolase ThsA, (2R,3R,3aS,5S,6R,7S,8R,11R,13S,15aR)-2-(6-amino-9H-purin-9-yl)-3,6,7,11,13-pentahydroxyoctahydro-2H,5H,11H,13H-5,8-epoxy-11lambda~5~,13lambda~5~-furo[2,3-g][1,3,5,9,2,4]tetraoxadiphosphacyclotetradecine-11,13-dione, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (3 entities in total) |
| Functional Keywords | thoeris, sir2 domain, slog domain, 3'cadpr, hydrolase |
| Biological source | Bacillus cereus MSX-D12 |
| Total number of polymer chains | 12 |
| Total formula weight | 679469.65 |
| Authors | Tamulaitiene, G.,Sasnauskas, G.,Sabonis, D. (deposition date: 2022-11-29, release date: 2024-02-21, Last modification date: 2024-04-03) |
| Primary citation | Tamulaitiene, G.,Sabonis, D.,Sasnauskas, G.,Ruksenaite, A.,Silanskas, A.,Avraham, C.,Ofir, G.,Sorek, R.,Zaremba, M.,Siksnys, V. Activation of Thoeris antiviral system via SIR2 effector filament assembly. Nature, 627:431-436, 2024 Cited by PubMed Abstract: To survive bacteriophage (phage) infections, bacteria developed numerous anti-phage defence systems. Some of them (for example, type III CRISPR-Cas, CBASS, Pycsar and Thoeris) consist of two modules: a sensor responsible for infection recognition and an effector that stops viral replication by destroying key cellular components. In the Thoeris system, a Toll/interleukin-1 receptor (TIR)-domain protein, ThsB, acts as a sensor that synthesizes an isomer of cyclic ADP ribose, 1''-3' glycocyclic ADP ribose (gcADPR), which is bound in the Smf/DprA-LOG (SLOG) domain of the ThsA effector and activates the silent information regulator 2 (SIR2)-domain-mediated hydrolysis of a key cell metabolite, NAD (refs. ). Although the structure of ThsA has been solved, the ThsA activation mechanism remained incompletely understood. Here we show that 1''-3' gcADPR, synthesized in vitro by the dimeric ThsB' protein, binds to the ThsA SLOG domain, thereby activating ThsA by triggering helical filament assembly of ThsA tetramers. The cryogenic electron microscopy (cryo-EM) structure of activated ThsA revealed that filament assembly stabilizes the active conformation of the ThsA SIR2 domain, enabling rapid NAD depletion. Furthermore, we demonstrate that filament formation enables a switch-like response of ThsA to the 1''-3' gcADPR signal. PubMed: 38383786DOI: 10.1038/s41586-024-07092-x PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.96 Å) |
Structure validation
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