8WKX

Cryo-EM structure of DSR2

Summary for 8WKX

• Entry DOI: 10.2210/pdb8wkx/pdb
• EMDB information: 37610
• Descriptor: SIR2-like domain-containing protein (1 entity in total)
• Functional Keywords: anti-phage immune, nadase, defense-associated sirtuin 2, dsr2, phage tail tube protein, dsr anti defense 1, dsad1, bacteria-phage interaction, surfactant protein
• Biological source: Bacillus subtilis subsp. natto (strain BEST195)
• Total number of polymer chains: 2
• Total formula weight: 237271.58

Authors

Gao, A.,Huang, J.,Zhu, K. (deposition date: 2023-09-28, release date: 2024-05-22)

Primary citation

Huang, J.,Zhu, K.,Gao, Y.,Ye, F.,Li, Z.,Ge, Y.,Liu, S.,Yang, J.,Gao, A.
Molecular basis of bacterial DSR2 anti-phage defense and viral immune evasion.
Nat Commun, 15:3954-3954, 2024

PubMed Abstract: Defense-associated sirtuin 2 (DSR2) systems are widely distributed across prokaryotic genomes, providing robust protection against phage infection. DSR2 recognizes phage tail tube proteins and induces abortive infection by depleting intracellular NAD, a process that is counteracted by another phage-encoded protein, DSR Anti Defense 1 (DSAD1). Here, we present cryo-EM structures of Bacillus subtilis DSR2 in its apo, Tube-bound, and DSAD1-bound states. DSR2 assembles into an elongated tetramer, with four NADase catalytic modules clustered in the center and the regulatory-sensing modules distributed at four distal corners. Interestingly, monomeric Tube protein, rather than its oligomeric states, docks at each corner of the DSR2 tetramer to form a 4:4 DSR2-Tube assembly, which is essential for DSR2 NADase activity. DSAD1 competes with Tube for binding to DSR2 by occupying an overlapping region, thereby inhibiting DSR2 immunity. Thus, our results provide important insights into the assembly, activation and inhibition of the DSR2 anti-phage defense system.

PubMed: 38729958
DOI: 10.1038/s41467-024-48291-4

Experimental method

ELECTRON MICROSCOPY (4.15 Å)