Author
Listed:
- Ruiwen Wang
(Central South University)
- Qi Xu
(Westlake University
Westlake Laboratory of Life Sciences and Biomedicine)
- Zhuoxi Wu
(Central South University)
- Jialu Li
(Westlake University
Westlake Laboratory of Life Sciences and Biomedicine)
- Hao Guo
(Central South University)
- Tianzhui Liao
(Central South University)
- Yuan Shi
(Westlake University
Westlake Laboratory of Life Sciences and Biomedicine)
- Ling Yuan
(Central South University)
- Haishan Gao
(Westlake University
Westlake Laboratory of Life Sciences and Biomedicine)
- Rong Yang
(Hunan Normal University)
- Zhubing Shi
(Westlake University
Westlake Laboratory of Life Sciences and Biomedicine)
- Faxiang Li
(Central South University)
Abstract
DSR2, a Sir2 domain-containing protein, protects bacteria from phage infection by hydrolyzing NAD+. The enzymatic activity of DSR2 is triggered by the SPR phage tail tube protein (TTP), while suppressed by the SPbeta phage-encoded DSAD1 protein, enabling phages to evade the host defense. However, the molecular mechanisms of activation and inhibition of DSR2 remain elusive. Here, we report the cryo-EM structures of apo DSR2, DSR2-TTP-NAD+ and DSR2-DSAD1 complexes. DSR2 assembles into a head-to-head tetramer mediated by its Sir2 domain. The C-terminal helical regions of DSR2 constitute four partner-binding cavities with opened and closed conformation. Two TTP molecules bind to two of the four C-terminal cavities, inducing conformational change of Sir2 domain to activate DSR2. Furthermore, DSAD1 competes with the activator for binding to the C-terminal cavity of DSR2, effectively suppressing its enzymatic activity. Our results provide the mechanistic insights into the DSR2-mediated anti-phage defense system and DSAD1-dependent phage immune evasion.
Suggested Citation
Ruiwen Wang & Qi Xu & Zhuoxi Wu & Jialu Li & Hao Guo & Tianzhui Liao & Yuan Shi & Ling Yuan & Haishan Gao & Rong Yang & Zhubing Shi & Faxiang Li, 2024.
"The structural basis of the activation and inhibition of DSR2 NADase by phage proteins,"
Nature Communications, Nature, vol. 15(1), pages 1-12, December.
Handle:
RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-50410-0
DOI: 10.1038/s41467-024-50410-0
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