Context-Dependent Heterotypic Assemblies of Intrinsically Disordered Peptides

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 14, 2025

Despite their critical role in context-dependent interactions for protein functions, intrinsically disordered regions (IDRs) are often overlooked designing peptide assemblies. Here, we exploit IDRs to enable heterotypic assemblies of peptides, where "context-dependent" refers assembly behavior driven by with other molecules. By attaching an aromatic segment oppositely charged achieve a nanofiber formation. Although the same-charged peptides cannot self-assemble, form nanofibers. Cryo-EM analysis reveals β-sheet arrangement within ordered core these nanofibers, conformational heterogeneity, and disorder-to-order continuum shows high number hydrogen bonds between tyrosine lysine ε-amine. Additionally, this work demonstrates post-assembly morphological change resulting from local flexibility. While equal molar mixtures yield doubling positively after produces bundles Furthermore, reducing amino acid residues reduces bundle Demonstrating self-assembly revealing atomistic insights into first time, illustrates straightforward approach self-assemble design adaptive, multifunctional nanomaterials.

Language: Английский

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Cytoplasmic mRNA decay controlling inflammatory gene expression is determined by pre-mRNA fate decision

Molecular Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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How energy determines spatial localisation and copy number of molecules in neurons

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 6, 2025

Abstract In neurons, the quantities of mRNAs and proteins are traditionally assumed to be determined by functional, electrical or genetic factors. Yet, there may also global, currently unknown computational rules that valid across different molecular species inside a cell. Surprisingly, our results show energy for turnover is significant cellular expense, en par with spiking cost, which requires energy-saving strategies. We drive save determines transcript their location while acting differently on each depending length, longevity other features respective molecule. combined own data experimental reports from five large-scale mRNA proteomics screens, comprising more than ten thousand reveal underlying principles localisation. found minimisation explain experimentally-reported exponential rank distributions protein copy numbers. Our further robust benefits when certain classes moved into dendrites, example long amino acid chains large non-coding regions half-lives proving surprising insights at level populations.

Language: Английский

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The ribosome as a platform to coordinate mRNA decay

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(4)

Published: Jan. 30, 2025

Messenger RNA (mRNA) homeostasis is a critical aspect of cellular function, involving the dynamic interplay between transcription and decay processes. Recent advances have revealed that ribosome plays central role in coordinating mRNA decay, challenging traditional view free primary substrate for degradation. This review examines mechanisms whereby ribosomes facilitate both licensing execution decay. involves factors such as Ccr4-Not complex, small MutS-related domain endonucleases, various quality control pathways. We discuss how translational fidelity, well presence nonoptimal codons collisions, can trigger pathways nonstop no-go Furthermore, we highlight direct association canonical exonucleases, Xrn1 Ski-exosome system, with ribosome, underscoring ribosome's multifaceted platform regulatory processes governing stability. By integrating recent findings, this offers comprehensive overview structural basis not only translation but also serve hubs coordination.

Language: Английский

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Deciphering Phase-Separated Mitochondrial RNA Granules under Stress Conditions with the Mitoribosome-Targeting Small Molecule

Analytical Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

RNA granules are liquid-liquid-phase-separated condensates comprising and proteins. Despite growing insights into their biological functions, studies have predominantly relied on methodologies lacking adequate chemical tools. Here, we introduce ICP-CHARGINGS, a concept for efficiently identifying probes to characterize of interest among nucleic acid-targeting agents. Focusing mitochondrial (MRGs), whose functions remain elusive, developed methodology within this framework identified NATA, new fluorescent molecule that, following mechanistic studies, was found bind the mitoribosome, enabling MRG labeling recognition. Using NATA reveal potential buffering roles MRGs, demonstrated close correlation between maintenance assembly cellular survival proliferation under cold shock hypoxic stress. Overall, introduction implementation ICP-CHARGINGS strategy provide specialized tool advancing our comprehension biology establish paradigm elucidating structures that can be targeted by small molecules, paving way developing tailored diverse in future research.

Language: Английский

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