PXD047450

PXD047450 is an original dataset announced via ProteomeXchange.

Title	Structure and mechanism of the Zorya anti-phage defense system
Description	Zorya is a recently identified and widely distributed bacterial immune system that protects bacteria from viral (phage) infections. Three Zorya subtypes have been discovered, each containing predicted membrane-embedded ZorAB complexes paired with soluble subunits that differ among Zorya subtypes, notably ZorC and ZorD in type I Zorya systems1,2. Here, we investigate the molecular basis of Zorya defense using cryo-electron microscopy, mutagenesis, fluorescence microscopy, proteomics, and functional studies. We present cryo-EM structures of ZorAB and show that it shares stoichiometry and features of other 5:2 inner membrane ion-driven rotary motors. The ZorA5B2 complex contains a dimeric ZorB peptidoglycan binding domain and a pentameric α-helical coiled-coil tail made of ZorA that projects approximately 70 nm into the cytoplasm. We also characterize the structure and function of the soluble Zorya components, ZorC and ZorD, finding that they harbour DNA binding and nuclease activity, respectively. Comprehensive functional and mutational analyses demonstrate that all Zorya components work in concert to protect bacterial cells against invading phages. We provide evidence that ZorAB operates as a proton-driven motor that becomes activated upon sensing of phage invasion. Subsequently, ZorAB transfers the phage invasion signal through the ZorA cytoplasmic tail to recruit and activate the soluble ZorC and ZorD effectors, which facilitate degradation of the phage DNA. In summary, our study elucidates the foundational mechanisms of Zorya function as an anti-phage defense system.
HostingRepository	PRIDE
AnnounceDate	2025-01-24
AnnouncementXML	Submission_2025-01-24_05:46:23.287.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ivo Hendriks
SpeciesList	scientific name: Escherichia coli; NCBI TaxID: 562;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Astral

Revision	Datetime	Status	ChangeLog Entry
0	2023-12-01 09:59:43	ID requested
⏵ 1	2025-01-24 05:46:23	announced

10.1038/S41586-024-08493-8;

submitter keyword: phage, phage defense system, bacterial immune system,Zorya, ion-driven motor

Ivo Hendriks
contact affiliation	Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact email	ivo.a.hendriks@gmail.com
lab head
Ivo Hendriks
contact affiliation	Proteomics program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen, Denmark
contact email	ivo.a.hendriks@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD047450
     1. Label: PRIDE project
     2. Name: Structure and mechanism of the Zorya anti-phage defense system