Target DNA-dependent activation mechanism of the prokaryotic immune system SPARTA DOI Creative Commons
Giada Finocchio, Balwina Koopal, Ana Potocnik

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(4), P. 2012 - 2029

Published: Jan. 15, 2024

In both prokaryotic and eukaryotic innate immune systems, TIR domains function as NADases that degrade the key metabolite NAD+ or generate signaling molecules. Catalytic activation of requires oligomerization, but how this is achieved varies in distinct systems. Short Argonaute (pAgo)/TIR-APAZ (SPARTA) system, NADase activity triggered upon guide RNA-mediated recognition invading DNA by an unknown mechanism. Here, we describe cryo-EM structures SPARTA inactive monomeric target DNA-activated tetrameric states. The structure reveals absence DNA, a C-terminal tail TIR-APAZ occupies nucleic acid binding cleft formed pAgo subunits, inhibiting activation. active complex, displaces induces conformational changes facilitate SPARTA-SPARTA dimerization. Concurrent release rotation one domain allow it to form composite catalytic site with other within dimer, self-complementary interface mediates cooperative tetramerization. Combined, study provides critical insights into structural architecture molecular mechanism underlying DNA-dependent oligomerization

Language: Английский

Structural basis of antiphage immunity generated by a prokaryotic Argonaute-associated SPARSA system DOI Creative Commons
Xiangkai Zhen, Xiaolong Xu, Le Ye

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 11, 2024

Argonaute (Ago) proteins are ubiquitous across all kingdoms of life. Eukaryotic Agos (eAgos) use small RNAs to recognize transcripts for RNA silencing in eukaryotes. In contrast, the functions prokaryotic counterparts (pAgo) less well known. Recently, short pAgos conjunction with associated TIR or Sir2 (SPARTA SPARSA) were found serve as antiviral systems combat phage infections. Herein, we present cryo-EM structures nicotinamide adenine dinucleotide (NAD

Language: Английский

Citations

15
Insights into the modulation of bacterial NADase activity by phage proteins DOI Creative Commons
Hang Yin, Xuzichao Li, Xiaoshen Wang

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 27, 2024

Abstract The Silent Information Regulator 2 (SIR2) protein is widely implicated in antiviral response by depleting the cellular metabolite NAD + . defense-associated sirtuin (DSR2) effector, a SIR2 domain-containing protein, protects bacteria from phage infection , while an anti-DSR2 (DSR anti-defense 1, DSAD1) employed some phages to evade this host defense. NADase activity of DSR2 unleashed recognizing tail tube (TTP). However, activation and inhibition mechanisms are unclear. Here, we determine cryo-EM structures multiple states. arranged as dimer dimers, which facilitated tetramerization domains. Moreover, assembly essential for activating function. activator TTP binding would trigger opening catalytic pocket decoupling N-terminal domain C-terminal (CTD) DSR2. Importantly, further show that mechanism conserved among other SIR2-dependent anti-phage systems. Interestingly, inhibitor DSAD1 mimics trap DSR2, thus occupying TTP-binding inhibiting Together, our results provide molecular insights into regulatory depletion immunity.

Language: Английский

Citations

14
Retron-Eco1 assembles NAD+-hydrolyzing filaments that provide immunity against bacteriophages DOI
Arturo Carabias, Sarah Camara-Wilpert, Mario Rodríguez Mestre

et al.

Molecular Cell, Journal Year: 2024, Volume and Issue: 84(11), P. 2185 - 2202.e12

Published: May 23, 2024

Language: Английский

Citations

13
Cytoplasmic calcium influx mediated by plant MLKLs confers TNL-triggered immunity DOI Creative Commons

Qiaochu Shen,

Keiichi Hasegawa,

Nicole Oelerich

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(4), P. 453 - 465.e6

Published: March 20, 2024

The plant homolog of vertebrate necroptosis inducer mixed-lineage kinase domain-like (MLKL) contributes to downstream steps in Toll-interleukin-1 receptor domain NLR (TNL)-receptor-triggered immunity. Here, we show that Arabidopsis MLKL1 (AtMLKL1) clusters into puncta at the plasma membrane upon TNL activation and this sub-cellular reorganization is dependent on signal transducer, EDS1. We find AtMLKLs confer TNL-triggered immunity parallel with RPW8-type HeLo-domain-containing NLRs (RNLs) AtMLKL N-terminal HeLo indispensable for both clustering. mediates cytoplasmic Ca

Language: Английский

Citations

12
Target DNA-dependent activation mechanism of the prokaryotic immune system SPARTA DOI Creative Commons
Giada Finocchio, Balwina Koopal, Ana Potocnik

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(4), P. 2012 - 2029

Published: Jan. 15, 2024

In both prokaryotic and eukaryotic innate immune systems, TIR domains function as NADases that degrade the key metabolite NAD+ or generate signaling molecules. Catalytic activation of requires oligomerization, but how this is achieved varies in distinct systems. Short Argonaute (pAgo)/TIR-APAZ (SPARTA) system, NADase activity triggered upon guide RNA-mediated recognition invading DNA by an unknown mechanism. Here, we describe cryo-EM structures SPARTA inactive monomeric target DNA-activated tetrameric states. The structure reveals absence DNA, a C-terminal tail TIR-APAZ occupies nucleic acid binding cleft formed pAgo subunits, inhibiting activation. active complex, displaces induces conformational changes facilitate SPARTA-SPARTA dimerization. Concurrent release rotation one domain allow it to form composite catalytic site with other within dimer, self-complementary interface mediates cooperative tetramerization. Combined, study provides critical insights into structural architecture molecular mechanism underlying DNA-dependent oligomerization

Language: Английский

Citations

11