8SXX

E. coli dodecamer SIR2

8SXX の概要

• エントリーDOI: 10.2210/pdb8sxx/pdb
• EMDBエントリー: 40860
• 分子名称: SIR2-like domain-containing protein, NICOTINAMIDE-ADENINE-DINUCLEOTIDE (2 entities in total)
• 機能のキーワード: sir2, nadase, nuclease, anti-phage system, immune system
• 由来する生物種: Escherichia coli
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 569773.07

構造登録者

Shen, Z.F.,Lin, Q.P.,Fu, T.M. (登録日: 2023-05-24, 公開日: 2023-12-27, 最終更新日: 2024-03-27)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.6 Å)