Molecular Cell, Journal Year: 2024, Volume and Issue: 84(17), P. 3172 - 3174
Published: Sept. 1, 2024
Language: Английский
Biochemical Journal, Journal Year: 2025, Volume and Issue: 482(05), P. 275 - 294
Published: March 1, 2025
The concept of higher-order assembly signalling or by co-operative formation (SCAF) was proposed based on the structures assemblies formed proteins featuring domains from death-fold family and Toll/interleukin-1 receptor domain family. Because these form filamentous upon stimulation activate downstream pathways through induced proximity, they were envisioned to sharpen response thresholds extreme co-operativity assembly. Recent findings demonstrate that a central feature SCAF mechanism is nucleation barrier allows switch-like, digital 'all-or-none' minute stimuli. In agreement, this features in cell-death innate immunity activation where binary decision required. Here, we broaden encapsulate essential kinetic properties open-ended signalling, compare other such as biomolecular condensates, review how operates cells.
Language: Английский
Citations
1
Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)
Published: March 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.
Language: Английский
Citations
1
Cell Research, Journal Year: 2025, Volume and Issue: unknown
Published: May 19, 2025
Language: Английский
Citations
0
Molecular Cell, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 1, 2024
Language: Английский
Citations
1
Cell Reports, Journal Year: 2024, Volume and Issue: 43(10), P. 114857 - 114857
Published: Oct. 1, 2024
Highlights•Phage-encoded DNA cytosine methyltransferase (Dcm) is a trigger of the retron Ec86 system•Dcm methylates stem-loop region msDNA to activate Ec86•Cryo-EM analysis reveals Ec86-effector filaments containing NAM and ADPr•The filament capable hydrolyzing NAD(P)+SummaryRetrons are class multigene antiphage defense systems typically consisting reverse transcriptase, non-coding RNA, cognate effector. Although triggers for several have been discovered recently, complete mechanism by which these detect invading phages mediate remains unclear. Here, we focus on system, elucidating its modes activation mechanisms action. We identified phage-encoded as system demonstrated that activated upon multicopy single-stranded (msDNA) methylation. further elucidated structure tripartite assembly primed Dcm nicotinamide adenine dinucleotide (NAD+). These findings provide insights into underscore an emerging theme through supramolecular complex assemblies.Graphical abstract
Language: Английский
Citations
1
Trends in Microbiology, Journal Year: 2024, Volume and Issue: unknown
Published: Oct. 1, 2024
HighlightsNoncoding RNAs (ncRNAs) have emerged as pivotal players in bacteria–phage conflicts.Many bacterial immune systems depend on ncRNAs for both structure and function.ncRNAs are key regulators of responses.Phages use to counteract defenses.AbstractThe evolutionary arms race between bacteria phages has driven the development diverse anti-phage defense mechanisms. Recent studies identified noncoding conflicts, including CRISPR-Cas, toxin–antitoxin (TA), reverse transcriptase (RT)-based defenses; however, our understanding their roles immunity is still emerging. In this review, we explore multifaceted immunity, offering insights into contributions anti-defense mechanisms, influence regulatory networks, potential biotechnological applications. Finally, highlight outstanding questions field spark future research directions.
Language: Английский
Citations
1
Molecular Cell, Journal Year: 2024, Volume and Issue: 84(17), P. 3172 - 3174
Published: Sept. 1, 2024
Language: Английский
Citations
0