Assembly-mediated activation of the SIR2-HerA supramolecular complex for anti-phage defense.

ABSTRACT: SIR2-HerA, a bacterial two-protein anti-phage defense system, induces bacterial death by depleting NAD⁺ upon phage infection. Biochemical reconstitution of SIR2, HerA, and the SIR2-HerA complex reveals a dynamic assembly process. Unlike other ATPases, HerA can form various oligomers, ranging from dimers to nonamers. When assembled with SIR2, HerA forms a hexamer and converts SIR2 from a nuclease to an NAD⁺ hydrolase, representing an unexpected regulatory mechanism mediated by protein assembly. Furthermore, high concentrations of ATP can inhibit NAD⁺ hydrolysis by the SIR2-HerA complex. Cryo-EM structures of the SIR2-HerA complex reveal a giant supramolecular assembly up to 1 MDa, with SIR2 as a dodecamer and HerA as a hexamer, crucial for anti-phage defense

SUBMITTER: Shen Z 

PROVIDER: S-EPMC11418745 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature