Hibernating ribosomes as drug targets? DOI Creative Commons
Chinenye L. Ekemezie, Sergey Melnikov

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: July 29, 2024

When ribosome-targeting antibiotics attack actively growing bacteria, they occupy ribosomal active centers, causing the ribosomes to stall or make errors that either halt cellular growth cause bacterial death. However, emerging research indicates spend a considerable amount of time in an inactive state known as ribosome hibernation, which dissociate from their substrates and bind specialized proteins called hibernation factors. Since 60% microbial biomass exists dormant at any given time, these factors are likely most common partners cells. Furthermore, some drug-binding sites - leading question how influences antibiotic efficacy, vice versa. In this review, we summarize current knowledge on physical functional interactions between explore possibility using target not only but also hibernating ribosomes. Because empowers bacteria withstand harsh conditions such starvation, stress, host immunity, line holds promise for medicine, agriculture, biotechnology: by learning regulate could enhance our capacity manage survival microorganisms dormancy.

Language: Английский

Nucleotide-induced hyper-oligomerization inactivates transcription termination factor ρ DOI Creative Commons
Bing Wang, Nelly Said, Tarek Hilal

et al.

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

Published: Feb. 15, 2025

Bacterial RNA helicase ρ is a genome sentinel that terminates the synthesis of damaged and junk RNAs are not translated by ribosome. It unclear how regulated during dormancy or stress, when translation inefficient vulnerable to ρ-mediated release. We use cryogenic electron microscopy, biochemical, genetic approaches show substitutions residues in connector between two domains ADP promote formation extended Escherichia coli filaments. By contrast, (p)ppGpp induces transient dodecamers. Our results demonstrate nucleotides bound at subunit interfaces inhibit ring closure underpins hexamer activation, thus favoring assembly inactive higher-order oligomers. Connector antibiotics protein syntheses trigger aggregation cell. These other recent data implicate as widespread strategy tune activity.

Language: Английский

Citations

0
Structure of an Archaeal Ribosome with a Divergent Active Site DOI Creative Commons
Amos J. Nissley, Yekaterina Shulgina,

Roan W. Kivimae

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 12, 2024

Abstract The ribosome is the universal translator of genetic code and shared across all life. Despite divergence in structure over course evolution, peptidyl transferase center (PTC), catalytic site ribosome, has been thought to be nearly universally conserved. Here, we identify clades archaea that have highly divergent ribosomal RNA sequences PTC. To understand how these PTC fold, determined cryo-EM structures Pyrobaculum calidifontis ribosome. We find sequence variation leads rearrangement key base triples differences between archaeal bacterial proteins also enable PTCs. Finally, a novel hibernation factor differs from known eukaryotic factors found multiple phyla. Overall, this work identifies regulate function reveals larger diversity most ancient

Language: Английский

Citations

0
Staphylococcal exoribonuclease YhaM destabilizes ribosomes by targeting the mRNA of a hibernation factor DOI Creative Commons
Anna Lipońska, Hyun Lee, Mee‐Ngan F. Yap

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: 52(15), P. 8998 - 9013

Published: July 9, 2024

Abstract The hibernation-promoting factor (Hpf) in Staphylococcus aureus binds to 70S ribosomes and induces the formation of 100S complex (70S dimer), leading translational avoidance occlusion from RNase R-mediated degradation. Here, we show that 3′-5′ exoribonuclease YhaM plays a previously unrecognized role modulating ribosome stability. Unlike R, which directly degrades 16S rRNA S. cells lacking Hpf, destabilizes by indirectly degrading 3′-hpf mRNA carries an intrinsic terminator. adopts active hexameric assembly robustly cleaves ssRNA manganese-dependent manner. In vivo, appears be low-processive enzyme, trimming hpf only 1 nucleotide. Deletion yhaM delays cell growth. These findings substantiate physiological significance this cryptic enzyme protective Hpf integrity, providing mechanistic understanding bacterial turnover.

Language: Английский

Citations

0
Hibernating ribosomes as drug targets? DOI Creative Commons
Chinenye L. Ekemezie, Sergey Melnikov

Frontiers in Microbiology, Journal Year: 2024, Volume and Issue: 15

Published: July 29, 2024

When ribosome-targeting antibiotics attack actively growing bacteria, they occupy ribosomal active centers, causing the ribosomes to stall or make errors that either halt cellular growth cause bacterial death. However, emerging research indicates spend a considerable amount of time in an inactive state known as ribosome hibernation, which dissociate from their substrates and bind specialized proteins called hibernation factors. Since 60% microbial biomass exists dormant at any given time, these factors are likely most common partners cells. Furthermore, some drug-binding sites - leading question how influences antibiotic efficacy, vice versa. In this review, we summarize current knowledge on physical functional interactions between explore possibility using target not only but also hibernating ribosomes. Because empowers bacteria withstand harsh conditions such starvation, stress, host immunity, line holds promise for medicine, agriculture, biotechnology: by learning regulate could enhance our capacity manage survival microorganisms dormancy.

Language: Английский

Citations

0