Mechanistic basis for the allosteric activation of NADase activity in the Sir2-HerA antiphage defense system

Xiangkai Zhen, Biao Zhou, Zihe Liu, Xurong Wang, Heyu Zhao, Shuxian Wu, Zekai Li, Jiamin Liang, Wanyue Zhang, Qingjian Zhu, Jun He (), Xiaoli Xiong () and Songying Ouyang ()
Additional contact information
Xiangkai Zhen: Fujian Normal University
Biao Zhou: Guangzhou Medical University
Zihe Liu: Fujian Normal University
Xurong Wang: Fujian Normal University
Heyu Zhao: Chinese Academy of Sciences
Shuxian Wu: Fujian Normal University
Zekai Li: Fujian Normal University
Jiamin Liang: Fujian Normal University
Wanyue Zhang: Fujian Normal University
Qingjian Zhu: Fujian Normal University
Jun He: Chinese Academy of Sciences
Xiaoli Xiong: Chinese Academy of Sciences
Songying Ouyang: Fujian Normal University

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53614-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53614-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53614-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().