Mechanistic basis for the allosteric activation of NADase activity in the Sir2-HerA antiphage defense system DOI Creative Commons
Xiangkai Zhen, Biao Zhou, Zihe Liu

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Окт. 27, 2024

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

Язык: Английский

A Comprehensive Resource for Exploring Antiphage Defense: DefenseFinder Webservice, Wiki and Databases. DOI Creative Commons
Florian Tesson, Rémi Planel, Artyom A. Egorov

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 26, 2024

In recent years, a vast number of novel antiphage defense mechanisms were uncovered. To facilitate the exploration mechanistic, ecological, and evolutionary aspects related to systems, we released DefenseFinder in 2021 (Tesson et al., 2022). is bioinformatic program designed for systematic identification known mechanisms. The initial release v1.0.0 included 60 systems. Over past three systems incorporated into has grown 152. increasing makes it challenge enter field interpretation detections difficult. Moreover, rapid development sequence-based predictions structures offers possibilities analysis should be easily available. overcome these challenges, present hub resources on including: 1) an updated version with web-service search function, 2) community-curated repository knowledge 3) precomputed databases, which include annotations done RefSeq genomes structure generated by AlphaFold. These pages can freely accessed users as starting point their journey better understand given system. We anticipate that will foster use bioinformatics study serve community researchers who This resource available at: https://defensefinder.mdmlab.fr.

Язык: Английский

Процитировано

15
Phages reconstitute NAD+ to counter bacterial immunity DOI
Ilya А. Osterman,

Hadar Samra,

François Rousset

и другие.

Nature, Год журнала: 2024, Номер 634(8036), С. 1160 - 1167

Опубликована: Сен. 25, 2024

Язык: Английский

Процитировано

15
A Comprehensive Resource for Exploring Antiphage Defense: DefenseFinder Webservice,Wiki and Databases DOI Creative Commons
Florian Tesson, Rémi Planel, Artyom A. Egorov

и другие.

Peer Community Journal, Год журнала: 2024, Номер 4

Опубликована: Сен. 25, 2024

Язык: Английский

Процитировано

13
Phages reconstitute NAD+to counter bacterial immunity DOI Creative Commons
Ilya А. Osterman,

Hadar Samra,

François Rousset

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 13, 2024

Abstract Bacteria defend against phage infection via a variety of antiphage defense systems. Many systems were recently shown to deplete cellular nicotinamide adenine dinucleotide (NAD + ) in response infection, by breaking NAD ADP-ribose (ADPR) and nicotinamide. It was demonstrated that depletion during deprives the from this essential molecule impedes replication. Here we show substantial fraction phages possess enzymatic pathways allowing reconstitution its degradation products infected cells. We describe pathway 1 (NARP1), two-step which one enzyme phosphorylates ADPR generate ADPR-pyrophosphate (ADPR-PP), second conjugates ADPR- PP . Phages encoding NARP1 can overcome diverse set systems, including Thoeris, DSR1, DSR2, SIR2-HerA, SEFIR, all as part their defensive mechanism. Phylogenetic analyses is primarily encoded on genomes, suggesting phage- specific function countering bacterial defenses. A pathway, NARP2, allows defenses building metabolites different than ADPR-PP. Our findings report unique immune evasion strategy where viruses rebuild molecules depleted thus overcoming host immunity.

Язык: Английский

Процитировано

6
Exploring the diversity of anti-defense systems across prokaryotes, phages and mobile genetic elements DOI Creative Commons
Florian Tesson, Erin Huiting,

Linlin Wei

и другие.

Nucleic Acids Research, Год журнала: 2024, Номер 53(1)

Опубликована: Дек. 9, 2024

Abstract The co-evolution of prokaryotes, phages and mobile genetic elements (MGEs) has driven the diversification defense anti-defense systems alike. Anti-defense proteins have diverse functional domains, sequences are typically small, creating a challenge to detect homologs across prokaryotic phage genomes. To date, no tools comprehensively annotate within desired sequence. Here, we developed ‘AntiDefenseFinder’—a free open-source tool web service that detects 156 one or more in any genomic Using this dataset, identified 47 981 distributed prokaryotes their viruses. We found some genes co-localize ‘anti-defense islands’, including Escherichia coli T4 Lambda phages, although many appear standalone. Eighty-nine per cent localize only preferentially MGE. However, >80% anti-Pycsar protein 1 (Apyc1) resides nonmobile regions bacterial Evolutionary analysis biochemical experiments revealed Apyc1 likely originated bacteria regulate cyclic nucleotide (cNMP) signaling, but co-opted overcome cNMP-utilizing defenses. With AntiDefenseFinder tool, hope facilitate identification full repertoire MGEs, discovery new functions deeper understanding host–pathogen arms race.

Язык: Английский

Процитировано

5
Activation of the bacterial defense-associated sirtuin system DOI Creative Commons
Kaixiang Zhu, Kun Shang,

Linyue Wang

и другие.

Communications Biology, Год журнала: 2025, Номер 8(1)

Опубликована: Фев. 24, 2025

The NADase activity of the defense-associated sirtuins (DSRs) is activated by phage tail tube protein (TTP). Herein, we report cryo-EM structures a free-state Bacillus subtilis DSR2 tetramer and fragment tetramer, SPR tube, two DSR2-TTP complexes. contains an N-terminal SIR2 domain, middle domain (MID) C-terminal (CTD). CTD harbors α-solenoid tandem-repeats like HEAT-repeat proteins. assembles into with four clustered at center, intertwined MID-CTD chains flank core. TTPs self-assemble tube-like complex. Upon binding, D1 TTP captured between HEAT-repeats domains DSR2, which conflicts self-assembly. Binding induces conformational changes in resulting increase NAD+ pocket volume SIR2, thus activates leads to cellular depletion. Cryo-EM reveal that sirtuin, recognizes protein, activating its elucidating role bacterial anti-phage immunity pathogen recognition.

Язык: Английский

Процитировано

0
Architecture remodeling activates the HerA-DUF anti-phage defense system DOI
Anthony D. Rish, Elizabeth Fosuah, Zhangfei Shen

и другие.

Molecular Cell, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
DUF4297 and HerA form abortosome to mediate bacterial immunity against phage infection DOI
Dongmei Tang, Ting Liu, Yijun Chen

и другие.

Molecular Cell, Год журнала: 2025, Номер unknown

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Filamentation activates bacterial Avs5 antiviral protein DOI Creative Commons
Yiqun Wang, Yuqing Tian, Xu Yang

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 11, 2025

Bacterial antiviral STANDs (Avs) are evolutionarily related to the nucleotide-binding oligomerization domain (NOD)-like receptors widely distributed in immune systems across animals and plants. EfAvs5, a type 5 Avs from Escherichia fergusonii, contains an N-terminal SIR2 effector domain, NOD, C-terminal sensor conferring protection against diverse phage invasions. Despite established roles of STAND prokaryotic eukaryotic immunity, mechanism underlying their collaboration remains unclear. Here we present cryo-EM structures EfAvs5 filaments, elucidating mechanisms dimerization, filamentation, filament bundling, ATP binding, NAD+ hydrolysis, all which crucial for anti-phage defense. The NOD domains engage intra- inter-dimer interaction form individual filament, while outward contribute bundle formation. Filamentation potentially stabilizes dimeric configuration, thereby activating NADase activity EfAvs5. Furthermore, identify nucleotide kinase gp1.7 T7 as activator demonstrating its ability induce filamentation activity. Together, uncover assembly Avs5 unique switch enzyme activities perform defenses. protect Here, authors reveal that forms clustered filaments hydrolysis can be activated by protein, mechanism.

Язык: Английский

Процитировано

0
Bacterial Hachiman complex executes DNA cleavage for antiphage defense DOI Creative Commons

Yongqing Cui,

Zhikang Dai, Yifang Ouyang

и другие.

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Март 17, 2025

Bacteria have developed a variety of immune systems to combat phage infections. The Hachiman system is novel prokaryotic antiphage defense comprising HamA and HamB proteins, which contains the DUF1837 helicase domains, respectively. However, mechanism remains only partially understood. Here, we present cryo-electron microscopy (cryo-EM) structure featuring fusion Cap4 nuclease domain within HamA. Further analysis indicates that on resembles PD-(D/E)XK but lacks active sites. Bioinformatics reveals catalytically inactive domains often recruit other functional fulfill anti-phage defense. interacts with form heterodimer HamAB mediate ATP hydrolysis execute DNA cleavage, thus implementing Our findings elucidate structural basis complex, highlighting critical roles in immunity. bacterial system. authors demonstrate type I-B functions as heterodimeric cooperate counteract infection.

Язык: Английский

Процитировано

0