8YHO

Cryo-EM structure of the trimeric HerA

8YHO の概要

• エントリーDOI: 10.2210/pdb8yho/pdb
• EMDBエントリー: 39290
• 分子名称: DUF87 domain-containing protein (1 entity in total)
• 機能のキーワード: antiphage system, immune system
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 195765.50

構造登録者

Zhen, X.,Xiong, X. (登録日: 2024-02-28, 公開日: 2024-11-13)

主引用文献

Zhen, X.,Zhou, B.,Liu, Z.,Wang, X.,Zhao, H.,Wu, S.,Li, Z.,Liang, J.,Zhang, W.,Zhu, Q.,He, J.,Xiong, X.,Ouyang, S.
Mechanistic basis for the allosteric activation of NADase activity in the Sir2-HerA antiphage defense system.
Nat Commun, 15:9269-9269, 2024

PubMed Abstract: Sir2-HerA is a widely distributed antiphage system composed of a RecA-like ATPase (HerA) and an effector with potential NADase activity (Sir2). Sir2-HerA is believed to provide defense against phage infection in Sir2-dependent NAD depletion to arrest the growth of infected cells. However, the detailed mechanism underlying its antiphage activity remains largely unknown. Here, we report functional investigations of Sir2-HerA from Staphylococcus aureus (SaSir2-HerA), unveiling that the NADase function of SaSir2 can be allosterically activated by the binding of SaHerA, which then assembles into a supramolecular complex with NADase activity. By combining the cryo-EM structure of SaSir2-HerA in complex with the NAD cleavage product, it is surprisingly observed that Sir2 protomers that interact with HerA are in the activated state, which is due to the opening of the α15-helix covering the active site, allowing NAD to access the catalytic pocket for hydrolysis. In brief, our study provides a comprehensive view of an allosteric activation mechanism for Sir2 NADase activity in the Sir2-HerA immune system.

PubMed: 39465277
DOI: 10.1038/s41467-024-53614-6

実験手法

ELECTRON MICROSCOPY (2.8 Å)