+Search query
-Structure paper
Title | The structural basis of the activation and inhibition of DSR2 NADase by phage proteins. |
---|---|
Journal, issue, pages | Nat Commun, Vol. 15, Issue 1, Page 6185, Year 2024 |
Publish date | Jul 23, 2024 |
Authors | Ruiwen Wang / Qi Xu / Zhuoxi Wu / Jialu Li / Hao Guo / Tianzhui Liao / Yuan Shi / Ling Yuan / Haishan Gao / Rong Yang / Zhubing Shi / Faxiang Li / |
PubMed 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 ...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. |
External links | Nat Commun / PubMed:39039073 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.11 - 4.14 Å |
Structure data | EMDB-38824, PDB-8y13: EMDB-38867: The Cryo-EM map of anti-phage defense associated DSR2 tetramer (H171A) EMDB-38868: Local refinement of anti-phage defense associated DSR2 tetramer (H171A) EMDB-38869: Local refinement of anti-phage defense associated DSR2 tetramer (H171A) EMDB-38870: The Cryo-EM map of anti-phage defense associated DSR2 (H171A) before local refinement (map2) EMDB-38871: Local refinement of anti-phage defense associated DSR2 (H171A) (map2) EMDB-38872, PDB-8y34: EMDB-38887: The Cryo-EM map of DSR2-DSAD1 complex (cross-linked) before local refinement EMDB-38888: Local refinement of DSR2-DSAD1 complex (cross-linked) EMDB-38889, PDB-8y3m: EMDB-38890: The Cryo-EM map of DSR2 tetramer bound with two DSAD1 inhibitor on the same side before local refinement EMDB-38891: Local refinement of DSR2 tetramer bound with two DSAD1 inhibitor on the same side EMDB-38901: Local refinement of DSR2 tetramer bound with two DSAD1 inhibitor on the same side EMDB-38902, PDB-8y3w: EMDB-38907, PDB-8y3y: EMDB-39912: The cryo-EM map of DSR2-tail tube-NAD complex before local refinement EMDB-39913: Local refinement of DSR2-tail tube-NAD+ complex EMDB-39914: Local refinement of DSR2-tail tube-NAD+ complex EMDB-39925, PDB-8zc9: |
Chemicals | ChemComp-NAD: |
Source |
|
Keywords | IMMUNE SYSTEM / NADase / anti-phage defense / tetramer / IMMUNOSUPPRESSANT / complex / immune evasion / tail-tube protein / NAD |