%0 Journal Article
%A Sabonis, Dziugas
%A Avraham, Carmel
%A Chang, Renee B.
%A Lu, Allen
%A Herbst, Ehud
%A Silanskas, Arunas
%A Vilutis, Deividas
%A Leavitt, Azita
%A Yirmiya, Erez
%A Toyoda, Hunter C.
%A Ruksenaite, Audrone
%A Zaremba, Mindaugas
%A Osterman, Ilya
%A Amitai, Gil
%A Kranzusch, Philip J.
%A Sorek, Rotem
%A Tamulaitiene, Giedre
%T TIR domains produce histidine-ADPR as an immune signal in bacteria
%J Nature
%V 642
%N 8067
%@ 0028-0836
%C London [u.a.]
%I Nature Publ. Group
%M PUBDB-2025-02291
%P 467 - 473
%D 2025
%Z Waiting for fulltext 
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40307559
%R 10.1038/s41586-025-08930-2
%U https://bib-pubdb1.desy.de/record/632963