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Title | Structural basis for phage-mediated activation and repression of bacterial DSR2 anti-phage defense system. |
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Journal, issue, pages | Nat Commun, Vol. 15, Issue 1, Page 2797, Year 2024 |
Publish date | Mar 30, 2024 |
Authors | Jun-Tao Zhang / Xiao-Yu Liu / Zhuolin Li / Xin-Yang Wei / Xin-Yi Song / Ning Cui / Jirui Zhong / Hongchun Li / Ning Jia / |
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 ...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. |
External links | Nat Commun / PubMed:38555355 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.49 - 3.62 Å |
Structure data | EMDB-37919, PDB-8wy8: EMDB-37920, PDB-8wy9: EMDB-37921, PDB-8wya: EMDB-37922, PDB-8wyb: EMDB-37923, PDB-8wyc: EMDB-37924, PDB-8wyd: EMDB-37925, PDB-8wye: EMDB-37926, PDB-8wyf: |
Chemicals | ChemComp-NAD: |
Source |
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Keywords | ANTIVIRAL PROTEIN / Phage defense proteins |