9CS8

Structure of Azospirillum bacterial CARD crystal form 2

Summary for 9CS8

• Entry DOI: 10.2210/pdb9cs8/pdb
• Descriptor: Serine protease (2 entities in total)
• Functional Keywords: anti-phage defense, caspase activation and recruitment domain, immune system
• Biological source: Azospirillum
• Total number of polymer chains: 4
• Total formula weight: 46608.76

Authors

Wein, T.,Millman, A.,Lange, K.,Yirmiya, E.,Hadary, R.,Garb, J.,Melamed, S.,Steinruecke, F.,Hill, A.B.,Kranzusch, P.J.,Sorek, R. (deposition date: 2024-07-23, release date: 2025-01-29, Last modification date: 2025-03-26)

Primary citation

Wein, T.,Millman, A.,Lange, K.,Yirmiya, E.,Hadary, R.,Garb, J.,Melamed, S.,Amitai, G.,Dym, O.,Steinruecke, F.,Hill, A.B.,Kranzusch, P.J.,Sorek, R.
CARD domains mediate anti-phage defence in bacterial gasdermin systems.
Nature, 639:727-734, 2025

PubMed Abstract: Caspase recruitment domains (CARDs) and pyrin domains are important facilitators of inflammasome activity and pyroptosis. Following pathogen recognition by nucleotide binding-domain, leucine-rich, repeat-containing (NLR) proteins, CARDs recruit and activate caspases, which, in turn, activate gasdermin pore-forming proteins to induce pyroptotic cell death. Here we show that CARD domains are present in defence systems that protect bacteria against phage. The bacterial CARD domain is essential for protease-mediated activation of certain bacterial gasdermins, which promote cell death once phage infection is recognized. We further show that multiple anti-phage defence systems use CARD domains to activate a variety of cell death effectors, and that CARD domains mediate protein-protein interactions in these systems. We find that these systems are triggered by a conserved immune-evasion protein used by phages to overcome the bacterial defence system RexAB, demonstrating that phage proteins inhibiting one defence system can activate another. Our results suggest that CARD domains represent an ancient component of innate immune systems conserved from bacteria to humans, and that CARD-dependent activation of gasdermins is shared in organisms across the tree of life.

PubMed: 39880956
DOI: 10.1038/s41586-024-08498-3

Experimental method

X-RAY DIFFRACTION (2.4 Å)