8SXX

E. coli dodecamer SIR2

Summary for 8SXX

• Entry DOI: 10.2210/pdb8sxx/pdb
• EMDB information: 40860
• Descriptor: SIR2-like domain-containing protein, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (2 entities in total)
• Functional Keywords: sir2, nadase, nuclease, anti-phage system, immune system
• Biological source: Escherichia coli
• Total number of polymer chains: 12
• Total formula weight: 569773.07

Authors

Shen, Z.F.,Lin, Q.P.,Fu, T.M. (deposition date: 2023-05-24, release date: 2023-12-27, Last modification date: 2024-03-27)

Primary citation

Shen, Z.,Lin, Q.,Yang, X.Y.,Fosuah, E.,Fu, T.M.
Assembly-mediated activation of the SIR2-HerA supramolecular complex for anti-phage defense.
Mol.Cell, 83:4586-4599.e5, 2023

PubMed 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. Unexpectedly, the HerA hexamer resembles a spiral staircase and exhibits helicase activities toward dual-forked DNA. Together, we reveal the supramolecular assembly of SIR2-HerA as a unique mechanism for switching enzymatic activities and bolstering anti-phage defense strategies.

PubMed: 38096827
DOI: 10.1016/j.molcel.2023.11.007

Experimental method

ELECTRON MICROSCOPY (3.6 Å)