Elsevier eBooks, Год журнала: 2024, Номер unknown, С. 419 - 428
Опубликована: Ноя. 29, 2024
Язык: Английский
Nature, Год журнала: 2025, Номер unknown
Опубликована: Фев. 12, 2025
Язык: Английский
Процитировано
3
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Янв. 3, 2024
Abstract TIR domains are central components of pattern recognition immune proteins across all life. In both bacteria and plants, TIR-domain were shown to recognize pathogen invasion then produce signaling molecules exclusively comprising nucleotide moieties. Here we show that the domain protein type II Thoeris defense system in produces a unique molecule amino acid histidine conjugated ADP-ribose (His-ADPR). His-ADPR is generated response phage infection activates cognate effector by binding Macro located at C-terminus protein. By determining crystal structure ligand-bound domain, describe structural basis for recognition. Our analyses furthermore reveal family bind sequester molecules, allowing phages evade TIR- mediated immunity. These data demonstrate diversity bacterial new class TIR-derived combining
Язык: Английский
Процитировано
15
Nature Communications, Год журнала: 2024, Номер 15(1)
Опубликована: Июнь 6, 2024
A short prokaryotic Argonaute (pAgo) TIR-APAZ (SPARTA) defense system, activated by invading DNA to unleash its TIR domain for NAD(P)
Язык: Английский
Процитировано
9
Proceedings of the National Academy of Sciences, Год журнала: 2025, Номер 122(2)
Опубликована: Янв. 9, 2025
Innate immunity relies on Toll-like receptors (TLRs) to detect pathogen-associated molecular patterns. The TIR (Toll/interleukin-1 receptor) domain-containing TLR adaptors TRIF (TIR adaptor-inducing interferon-β) and TRAM (TRIF-related adaptor molecule) are essential for MyD88-independent signaling. However, the structural basis of domain-based signaling remains unclear. Here, we present cryo-EM structures filaments formed by domains at resolutions 3.3 Å 5.6 Å, respectively. Both reveal two-stranded parallel helical arrangements. Functional studies underscore importance intrastrand interactions, mediated BB-loop, interstrand interactions in TLR4-mediated We also report crystal structure monomeric domain bearing BB loop mutation C117H, which reveals conformational differences consistent with its inactivity. Our findings suggest a unified mechanism four MyD88, MAL, TRIF, potential therapeutic targets immunity-related disorders.
Язык: Английский
Процитировано
1
Biochemical Journal, Год журнала: 2025, Номер 482(05), С. 275 - 294
Опубликована: Март 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.
Язык: Английский
Процитировано
1
Nature, Год журнала: 2025, Номер unknown
Опубликована: Апрель 30, 2025
Язык: Английский
Процитировано
1
Science Advances, Год журнала: 2024, Номер 10(26)
Опубликована: Июнь 26, 2024
Thoeris defense systems protect bacteria from infection by phages via abortive infection. In these systems, ThsB proteins serve as sensors of and generate signaling nucleotides that activate ThsA effectors. Silent information regulator SMF/DprA-LOG (SIR2-SLOG) containing effectors are activated cyclic ADP-ribose (ADPR) isomers 2'cADPR 3'cADPR, triggering nicotinamide adenine dinucleotide (NAD
Язык: Английский
Процитировано
4
Seminars in Cell and Developmental Biology, Год журнала: 2024, Номер 164, С. 1 - 12
Опубликована: Май 31, 2024
Transposable elements (TEs) provide a prime example of genetic conflict because they can proliferate in genomes and populations even if harm the host. However, numerous studies have shown that TEs, though typically harmful, also fuel for adaptation. This is code functional sequences be useful host which reside. In this review, I summarize "how" "why" adaptation enabled by between TEs hosts. addition, focusing on mechanisms TE control small piwi-interacting RNAs (piRNAs), highlight an indirect form conflict. case, defense regulate been redeployed endogenous gene regulation. propose released meiosis early eukaryotes may important because, among other reasons, it spurred evolutionary innovation multiple interwoven trajectories - part hosts embedded parasites. evolution function as complexity generating engine was critical player eukaryotic evolution.
Язык: Английский
Процитировано
3
Structure, Год журнала: 2025, Номер unknown
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
Science, Год журнала: 2025, Номер 388(6745), С. 415 - 422
Опубликована: Апрель 24, 2025
Protein polymer scaffolds composed of death fold (DF) proteins are critical to the formation signalosomes in immune signaling. The biophysical properties that these polymeric require for signal transduction not clearly defined. Here, we engineered single-component DF signalosomes. We found functionality depends on stability provided by polymer, which could also be achieved with a bacterial domain, synthetic filament-forming and amyloid-like sequences. This demonstrates importance inducibility irrespective motif's origin. By varying number included TRAF6 interaction motifs, demonstrate avidity is tunable property can control amplitude signaling outputs. work lays out reductionist framework elucidate required through adjusting their assembly kinetics, stability, avidity.
Язык: Английский
Процитировано
0