EMD-38869

Single-particle
3.52 Å
EMD-38869 Deposition: 28/01/2024
Map released: 11/09/2024
Last modified: 11/09/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-38869

Local refinement of anti-phage defense associated DSR2 tetramer (H171A)

EMD-38869

Single-particle
3.52 Å
EMD-38869 Deposition: 28/01/2024
Map released: 11/09/2024
Last modified: 11/09/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Bacillus subtilis
Sample: bacterial anti-phage defense associated DSR2 homo-tetramer

Deposition Authors: Li FX, Shi ZB, Wang RW, Xu Q , Yang R , Wu ZX
The structural basis of the activation and inhibition of DSR2 NADase by phage proteins.
Wang R, Xu Q , Wu Z, Li J, Guo H, Liao T, Shi Y, Yuan L, Gao H , Yang R , Shi Z , Li F
(2024) Nat Commun , 15 , 6185 - 6185
PUBMED: 39039073
DOI: doi:10.1038/s41467-024-50410-0
ISSN: 2041-1723
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.