8UAF

E. coli Sir2_HerA complex (12:6) bound with NAD+

This is a non-PDB format compatible entry.

Summary for 8UAF

• Entry DOI: 10.2210/pdb8uaf/pdb
• EMDB information: 42062
• Descriptor: SIR2-like domain-containing protein, Nucleoside triphosphate hydrolase, [(2R,3S,4R,5R)-5-(6-AMINOPURIN-9-YL)-3,4-DIHYDROXY-OXOLAN-2-YL]METHYL [HYDROXY-[[(2R,3S,4R,5S)-3,4,5-TRIHYDROXYOXOLAN-2-YL]METHOXY]PHOSPHORYL] HYDROGEN PHOSPHATE, ... (6 entities in total)
• Functional Keywords: hera, sir2, nadase, atpase, anti-phage system, immune system
• Biological source: Escherichia coli; More
• Total number of polymer chains: 18
• Total formula weight: 982206.11

Authors

Shen, Z.F.,Lin, Q.P.,Fu, T.M. (deposition date: 2023-09-20, 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 (3.18 Å)