8V3E

Structure of Myroides odoratus phage Tad2 in apo state

Summary for 8V3E

• Entry DOI: 10.2210/pdb8v3e/pdb
• Descriptor: Tad2 (2 entities in total)
• Functional Keywords: his-adpr, phage, anti-defense, sequestration, viral protein
• Biological source: Myroides odoratus
• Total number of polymer chains: 4
• Total formula weight: 39624.61

Authors

Lu, A.,Kranzusch, P.J. (deposition date: 2023-11-27, release date: 2025-04-30, Last modification date: 2025-06-25)

Primary citation

Sabonis, D.,Avraham, C.,Chang, R.B.,Lu, A.,Herbst, E.,Silanskas, A.,Vilutis, D.,Leavitt, A.,Yirmiya, E.,Toyoda, H.C.,Ruksenaite, A.,Zaremba, M.,Osterman, I.,Amitai, G.,Kranzusch, P.J.,Sorek, R.,Tamulaitiene, G.
TIR domains produce histidine-ADPR as an immune signal in bacteria.
Nature, 642:467-473, 2025

PubMed Abstract: Toll/interleukin-1 receptor (TIR) domains are central components of pattern recognition immune proteins across all domains of life. In bacteria and plants, TIR-domain proteins recognize pathogen invasion and then produce immune signalling molecules exclusively comprising nucleotide moieties. 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.

PubMed: 40307559
DOI: 10.1038/s41586-025-08930-2

Experimental method

X-RAY DIFFRACTION (2.39 Å)