8WY8

Cryo-EM structure of DSR2 apo complex

Summary for 8WY8

• Entry DOI: 10.2210/pdb8wy8/pdb
• EMDB information: 37919
• Descriptor: SIR2 family protein (1 entity in total)
• Functional Keywords: phage defense proteins, antiviral protein
• Biological source: Bacillus subtilis
• Total number of polymer chains: 4
• Total formula weight: 474543.16

Authors

Zhang, J.T.,Jia, N.,Liu, X.Y. (deposition date: 2023-10-30, release date: 2024-04-10, Last modification date: 2024-04-17)

Primary citation

Zhang, J.T.,Liu, X.Y.,Li, Z.,Wei, X.Y.,Song, X.Y.,Cui, N.,Zhong, J.,Li, H.,Jia, N.
Structural basis for phage-mediated activation and repression of bacterial DSR2 anti-phage defense system.
Nat Commun, 15:2797-2797, 2024

PubMed Abstract: Silent information regulator 2 (Sir2) proteins typically catalyze NAD-dependent protein deacetylation. The recently identified bacterial Sir2 domain-containing protein, defense-associated sirtuin 2 (DSR2), recognizes the phage tail tube and depletes NAD to abort phage propagation, which is counteracted by the phage-encoded DSR anti-defense 1 (DSAD1), but their molecular mechanisms remain unclear. Here, we determine cryo-EM structures of inactive DSR2 in its apo form, DSR2-DSAD1 and DSR2-DSAD1-NAD, as well as active DSR2-tube and DSR2-tube-NAD complexes. DSR2 forms a tetramer with its C-terminal sensor domains (CTDs) in two distinct conformations: CTD or CTD. Monomeric, rather than oligomeric, tail tube proteins preferentially bind to CTD and activate Sir2 for NAD hydrolysis. DSAD1 binding to CTD allosterically inhibits tube binding and tube-mediated DSR2 activation. Our findings provide mechanistic insight into DSR2 assembly, tube-mediated DSR2 activation, and DSAD1-mediated inhibition and NAD substrate catalysis in bacterial DSR2 anti-phage defense systems.

PubMed: 38555355
DOI: 10.1038/s41467-024-47177-9

Experimental method

ELECTRON MICROSCOPY (3.1 Å)