Structural basis for phage-mediated activation and repression of bacterial DSR2 anti-phage defense system

Zhang，Jun Tao1; Liu，Xiao Yu1; Li，Zhuolin1; Wei，Xin Yang1; Song，Xin Yi1; Cui，Ning1,2,3; Zhong，Jirui4,5; Li，Hongchun4,5; Jia，Ning1,2,3

2024-12-01

10.1038/s41467-024-47177-9

Nature Communications   影响因子和分区

2041-1723

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.

SCI

英语

第一 ; 通讯

2-s2.0-85188999492

Scopus

1.Department of Biochemistry,School of Medicine,Southern University of Science and Technology,Shenzhen,518055,China
2.Shenzhen Key Laboratory of Cell Microenvironment,Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research,Southern University of Science and Technology,Shenzhen,518055,China
3.Key University Laboratory of Metabolism and Health of Guangdong,Institute for Biological Electron Microscopy,Southern University of Science and Technology,Shenzhen,518055,China
4.Research Center for Computer-Aided Drug Discovery,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen,518055,China
5.Biomedicial Department,University of Chinese Academy of Sciences,Beijing,100049,China

Zhang，Jun Tao,Liu，Xiao Yu,Li，Zhuolin,et al. Structural basis for phage-mediated activation and repression of bacterial DSR2 anti-phage defense system[J]. Nature Communications,2024,15(1).

Zhang，Jun Tao.,Liu，Xiao Yu.,Li，Zhuolin.,Wei，Xin Yang.,Song，Xin Yi.,...&Jia，Ning.(2024).Structural basis for phage-mediated activation and repression of bacterial DSR2 anti-phage defense system.Nature Communications,15(1).

Zhang，Jun Tao,et al."Structural basis for phage-mediated activation and repression of bacterial DSR2 anti-phage defense system".Nature Communications 15.1(2024).