9EIB
Structure of Myroides odoratus prophage anti-Thoeris 2 (ModTad2) in complex with hisADPR
Summary for 9EIB
| Entry DOI | 10.2210/pdb9eib/pdb |
| Related | 8R66 8V3E |
| Descriptor | Prophage anti-Thoeris 2 (ModTad2), (2~{S})-3-[1-[(2~{R},3~{R},4~{S},5~{R})-5-[[[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-3,4-bis(oxidanyl)oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-oxidanyl-phosphoryl]oxymethyl]-3,4-bis(oxidanyl)oxolan-2-yl]imidazol-4-yl]-2-azanyl-propanoic acid (3 entities in total) |
| Functional Keywords | anti-thoeris, immune evasion, viral sponge, viral protein |
| Biological source | Myroides odoratus |
| Total number of polymer chains | 2 |
| Total formula weight | 20682.92 |
| Authors | Chang, R.B.,Kranzusch, P.J. (deposition date: 2024-11-25, release date: 2025-04-16, 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 Cited by 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: 40307559DOI: 10.1038/s41586-025-08930-2 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.67 Å) |
Structure validation
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