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Structure paper

TitleStructural basis for phage-mediated activation and repression of bacterial DSR2 anti-phage defense system.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 2797, Year 2024
Publish dateMar 30, 2024
AuthorsJun-Tao Zhang / Xiao-Yu Liu / Zhuolin Li / Xin-Yang Wei / Xin-Yi Song / Ning Cui / Jirui Zhong / Hongchun Li / Ning Jia /
PubMed AbstractSilent 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 linksNat Commun / PubMed:38555355 / PubMed Central
MethodsEM (single particle)
Resolution2.49 - 3.62 Å
Structure data

37919

8wy8

EMDB-37919, PDB-8wy8:
Cryo-EM structure of DSR2 apo complex
Method: EM (single particle) / Resolution: 3.1 Å

37920

8wy9

EMDB-37920, PDB-8wy9:
Cryo-EM structure of DSR2 apo (partial) complex
Method: EM (single particle) / Resolution: 2.57 Å

37921

8wya

EMDB-37921, PDB-8wya:
Cryo-EM structure of DSR2-tube complex
Method: EM (single particle) / Resolution: 3.62 Å

37922

8wyb

EMDB-37922, PDB-8wyb:
Cryo-EM structure of DSR2 (H171A)-tube-NAD+ complex
Method: EM (single particle) / Resolution: 3.37 Å

37923

8wyc

EMDB-37923, PDB-8wyc:
Cryo-EM structure of DSR2 (H171A)-tube-NAD+ (partial) complex
Method: EM (single particle) / Resolution: 3.0 Å

37924

8wyd

EMDB-37924, PDB-8wyd:
Cryo-EM structure of DSR2-DSAD1 complex
Method: EM (single particle) / Resolution: 2.56 Å

37925

8wye

EMDB-37925, PDB-8wye:
Cryo-EM structure of DSR2-DSAD1 (partial) complex
Method: EM (single particle) / Resolution: 2.49 Å

37926

8wyf

EMDB-37926, PDB-8wyf:
Cryo-EM structure of DSR2-DSAD1-NAD+ (partial) complex
Method: EM (single particle) / Resolution: 2.85 Å

Chemicals

ChemComp-NAD:
NICOTINAMIDE-ADENINE-DINUCLEOTIDE / NAD*YM / Nicotinamide adenine dinucleotide

Source
  • bacillus subtilis (bacteria)
  • bacillus phage spbc2 (virus)
  • bacillus phage spr (virus)
KeywordsANTIVIRAL PROTEIN / Phage defense proteins

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