7UAV

Structure of Clostridium botulinum prophage Tad1 in apo state

Summary for 7UAV

• Entry DOI: 10.2210/pdb7uav/pdb
• Descriptor: ABC transporter ATPase (2 entities in total)
• Functional Keywords: anti-thoeris, immune evasion, signal sequestration, viral protein
• Biological source: Clostridium botulinum
• Total number of polymer chains: 5
• Total formula weight: 72593.30

Authors

Lu, A.,Leavitt, A.,Yirmiya, E.,Amitai, G.,Garb, J.,Morehouse, B.R.,Hobbs, S.J.,Sorek, R.,Kranzusch, P.J. (deposition date: 2022-03-14, release date: 2022-10-05, Last modification date: 2024-10-16)

Primary citation

Leavitt, A.,Yirmiya, E.,Amitai, G.,Lu, A.,Garb, J.,Herbst, E.,Morehouse, B.R.,Hobbs, S.J.,Antine, S.P.,Sun, Z.J.,Kranzusch, P.J.,Sorek, R.
Viruses inhibit TIR gcADPR signalling to overcome bacterial defence.
Nature, 611:326-331, 2022

PubMed Abstract: The Toll/interleukin-1 receptor (TIR) domain is a key component of immune receptors that identify pathogen invasion in bacteria, plants and animals. In the bacterial antiphage system Thoeris, as well as in plants, recognition of infection stimulates TIR domains to produce an immune signalling molecule whose molecular structure remains elusive. This molecule binds and activates the Thoeris immune effector, which then executes the immune function. We identified a large family of phage-encoded proteins, denoted here as Thoeris anti-defence 1 (Tad1), that inhibit Thoeris immunity. We found that Tad1 proteins are 'sponges' that bind and sequester the immune signalling molecule produced by TIR-domain proteins, thus decoupling phage sensing from immune effector activation and rendering Thoeris inactive. Tad1 can also efficiently sequester molecules derived from a plant TIR-domain protein, and a high-resolution crystal structure of Tad1 bound to a plant-derived molecule showed a unique chemical structure of 1 ''-2' glycocyclic ADPR (gcADPR). Our data furthermore suggest that Thoeris TIR proteins produce a closely related molecule, 1''-3' gcADPR, which activates ThsA an order of magnitude more efficiently than the plant-derived 1''-2' gcADPR. Our results define the chemical structure of a central immune signalling molecule and show a new mode of action by which pathogens can suppress host immunity.

PubMed: 36174646
DOI: 10.1038/s41586-022-05375-9

Experimental method

X-RAY DIFFRACTION (2.2 Å)