8Y3Y

The Cryo-EM structure of anti-phage defense associated DSR2 tetramer bound with two DSAD1 inhibitors (opposite side)

8Y3Y の概要

• エントリーDOI: 10.2210/pdb8y3y/pdb
• EMDBエントリー: 38907
• 分子名称: SIR2-like domain-containing protein, DSR anti-defence 1 (2 entities in total)
• 機能のキーワード: nadase, anti-phage defense, complex, immune evasion, immunosuppressant
• 由来する生物種: Bacillus subtilis; 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 502289.02

構造登録者

Wang, R.W.,Xu, Q.,Wu, Z.X.,Li, J.L.,Shi, Z.B.,Li, F.X. (登録日: 2024-01-29, 公開日: 2024-09-11)

主引用文献

Wang, R.,Xu, Q.,Wu, Z.,Li, J.,Guo, H.,Liao, T.,Shi, Y.,Yuan, L.,Gao, H.,Yang, R.,Shi, Z.,Li, F.
The structural basis of the activation and inhibition of DSR2 NADase by phage proteins.
Nat Commun, 15:6185-6185, 2024

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 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.

PubMed: 39039073
DOI: 10.1038/s41467-024-50410-0

実験手法

ELECTRON MICROSCOPY (3.33 Å)