TY  - JOUR
AU  - Tamulaitiene, Giedre
AU  - Sabonis, Dziugas
AU  - Sasnauskas, Giedrius
AU  - Ruksenaite, Audrone
AU  - Silanskas, Arunas
AU  - Avraham, Carmel
AU  - Ofir, Gal
AU  - Sorek, Rotem
AU  - Zaremba, Mindaugas
AU  - Siksnys, Virginijus
TI  - Activation of Thoeris antiviral system via SIR2 effector filament assembly
JO  - Nature
VL  - 627
IS  - 8003
SN  - 0028-0836
CY  - London [u.a.]
PB  - Nature Publ. Group
M1  - PUBDB-2024-01566
SP  - 431-436
PY  - 2024
N1  - Waiting for fulltext 
AB  - To survive bacteriophage (phage) infections, bacteria developed numerous anti-phage defence systems1,2,3,4,5,6,7. 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 components8,9,10,11,12. 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. 12,13,14). Although the structure of ThsA has been solved15, 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:38383786
UR  - <Go to ISI:>//WOS:001173409400007
DO  - DOI:10.1038/s41586-024-07092-x
UR  - https://bib-pubdb1.desy.de/record/605884
ER  -