8y3y

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

spinqualitylabelsall models 8y3y, resolution 3.33Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8y3y is a 6 chain structure with sequence from Bacillus subtilis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.33Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function D4G637_BACNB Publication Abstract from PubMed 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. 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 Nat Commun. 2024 Jul 23;15(1):6185. doi: 10.1038/s41467-024-50410-0. PMID:39039073 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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