TY  - JOUR
AU  - Sabonis, Dziugas
AU  - Avraham, Carmel
AU  - Chang, Renee B.
AU  - Lu, Allen
AU  - Herbst, Ehud
AU  - Silanskas, Arunas
AU  - Vilutis, Deividas
AU  - Leavitt, Azita
AU  - Yirmiya, Erez
AU  - Toyoda, Hunter C.
AU  - Ruksenaite, Audrone
AU  - Zaremba, Mindaugas
AU  - Osterman, Ilya
AU  - Amitai, Gil
AU  - Kranzusch, Philip J.
AU  - Sorek, Rotem
AU  - Tamulaitiene, Giedre
TI  - TIR domains produce histidine-ADPR as an immune signal in bacteria
JO  - Nature
VL  - 642
IS  - 8067
SN  - 0028-0836
CY  - London [u.a.]
PB  - Nature Publ. Group
M1  - PUBDB-2025-02291
SP  - 467 - 473
PY  - 2025
N1  - Waiting for fulltext 
AB  - Toll/interleukin-1 receptor (TIR) domains are central components of pattern recognition immune proteins across all domains of life1,2. In bacteria and plants, TIR-domain proteins recognize pathogen invasion and then produce immune signalling molecules exclusively comprising nucleotide moieties2,3,4,5. Here we show that the TIR-domain protein of the type II Thoeris defence system in bacteria produces a unique signalling molecule comprising the amino acid histidine conjugated to ADP-ribose (His-ADPR). His-ADPR is generated in response to phage infection and activates the cognate Thoeris effector by binding a Macro domain located at the C terminus of the effector protein. By determining the crystal structure of a ligand-bound Macro domain, we describe the structural basis for His-ADPR and its recognition and show its role by biochemical and mutational analyses. Our analyses furthermore reveal a family of phage proteins that bind and sequester His-ADPR signalling molecules, enabling phages to evade TIR-mediated immunity. These data demonstrate diversity in bacterial TIR signalling and reveal a new class of TIR-derived immune signalling molecules that combine nucleotide and amino acid moieties.
LB  - PUB:(DE-HGF)16
C6  - pmid:40307559
DO  - DOI:10.1038/s41586-025-08930-2
UR  - https://bib-pubdb1.desy.de/record/632963
ER  -