+Open data
-Basic information
Entry | Database: PDB / ID: 8btp | ||||||
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Title | Helical structure of BcThsA in complex with 1''-3'gc(etheno)ADPR | ||||||
Components | NAD(+) hydrolase ThsA | ||||||
Keywords | HYDROLASE / Thoeris / SIR2 domain / SLOG domain / 3'cADPR | ||||||
Function / homology | Function and homology information NAD+ glycohydrolase / defense response to virus / hydrolase activity / nucleotide binding / cytoplasm Similarity search - Function | ||||||
Biological species | Bacillus cereus MSX-D12 (bacteria) | ||||||
Method | ELECTRON MICROSCOPY / helical reconstruction / cryo EM / Resolution: 2.75 Å | ||||||
Authors | Tamulaitiene, G. / Sasnauskas, G. / Sabonis, D. | ||||||
Funding support | Lithuania, 1items
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Citation | Journal: Nature / Year: 2024 Title: Activation of Thoeris antiviral system via SIR2 effector filament assembly. Authors: Giedre Tamulaitiene / Dziugas Sabonis / Giedrius Sasnauskas / Audrone Ruksenaite / Arunas Silanskas / Carmel Avraham / Gal Ofir / Rotem Sorek / Mindaugas Zaremba / Virginijus Siksnys / 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: ...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. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8btp.cif.gz | 985.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb8btp.ent.gz | 820.4 KB | Display | PDB format |
PDBx/mmJSON format | 8btp.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8btp_validation.pdf.gz | 2.6 MB | Display | wwPDB validaton report |
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Full document | 8btp_full_validation.pdf.gz | 2.7 MB | Display | |
Data in XML | 8btp_validation.xml.gz | 157.9 KB | Display | |
Data in CIF | 8btp_validation.cif.gz | 230.9 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/bt/8btp ftp://data.pdbj.org/pub/pdb/validation_reports/bt/8btp | HTTPS FTP |
-Related structure data
Related structure data | 16234MC 8btnC 8btoC C: citing same article (ref.) M: map data used to model this data |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
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Noncrystallographic symmetry (NCS) | NCS domain:
NCS domain segments:
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