Hibernation factor

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The structure of a Psychrobacter urativorans ribosome in a complex with the hibernation factors Balon and RaiA P. urativorans 70S ribosome with Balon and RaiA.jpg
The structure of a Psychrobacter urativorans ribosome in a complex with the hibernation factors Balon and RaiA

A hibernation factor is a protein used by cells to induce a dormant state by slowing or halting the cellular metabolism. [1] This can occur during periods of stress, [1] randomly in order to allocate "designated survivors" in a population, [1] or when bacteria cease growth (enter stationary phase). [2] Hibernation factors can do a variety of things, including dismantling cellular machinery and halting gene expression, but the most important hibernation factors bind to the ribosome and halt protein production, which consumes a large fraction of the energy in a cell. [1] [2]

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How different hibernation factors bind to the ribosome's active sites Balon RaiA RMF Binding.jpg
How different hibernation factors bind to the ribosome's active sites

Ribosome hibernation

Ribosome hibernation occurs when ribosome hibernation factors bind to the ribosome and halt protein production. Ribosome hibernation is almost ubiquitous in bacteria, as well as in the plastids of plants, and may also be present in eukaryotes. [2] Ribosome hibernation factors can simply inactivate ribosomes, (RaiA) link pairs into inactive dimers, like 100S ribosomes, (RMF and HPF) or interfere at various stages of the translation cycle (RsfS, YqjD, SRA, and EttA). [2] [3] One indicator of ribosome hibernation is the presence of a large number of 100S ribosomes, which can constitute up to 60% of the ribosomes in a cell at a times. [2]

RMF, RaiA, and HPF

Three proteins, RMF, RaiA, and HPF, are only found in the large class of bacteria gammaproteobacteria. [2] RMF (Ribosome modulation factor) is a small protein, typically produced under nutrient starvation and stress conditions, [4] that is the main factor in the formation of 100S ribosomes. [2] During the formation process, RMF binds together 70S (standard) ribosomes to form 90S ribosome dimers. [2] These 90S dimers are converted by HPF (hibernation promoting factor) to form mature 100S dimers. [2] A third protein, RaiA (ribosome-associated inhibitor A) is thought to both inactivate 70S ribosomes alone and stabilize them, preventing them from being converted into 100S ribosomes. [2] Most non-gammaproteobacteria, as well as some plant plastids, instead contain a HPF homologue that can form 100S ribosomes by itself. [2]

Balon

Balon (Spanish "ball", after homologue Pelota) [5] is a hibernation factor protein found in the cold-adapted bacterium Psychrobacter urativorans. [5] The protein was discovered accidentally by a researcher who unintentionally left a sample of P. urativorans in an ice bucket for too long, cold-shocking it, through subsequent cryo-EM scans of the organism's ribosomes. [1] Unlike other factors, Balon can bind to the ribosome while protein production is in process. [1] This is important for rapid response to stress because in some cells, protein production can take up to 20 minutes to complete. [6] Balon does this by rather than physically blocking the A site of the ribosome, as other hibernation factors do, binding near to but not across the channel, allowing it to attach to the ribosome independent of whether protein production is taking place. [1] Genetic relatives of Balon have been found in 20% of bacterial genomes catalogued in public databases, but are absent from Escherichia coli and Staphylococcus aureus , the most widely used models for cellular dormancy. [1]

Related Research Articles

<span class="mw-page-title-main">Lambda phage</span> Bacteriophage that infects Escherichia coli

Enterobacteria phage λ is a bacterial virus, or bacteriophage, that infects the bacterial species Escherichia coli. It was discovered by Esther Lederberg in 1950. The wild type of this virus has a temperate life cycle that allows it to either reside within the genome of its host through lysogeny or enter into a lytic phase, during which it kills and lyses the cell to produce offspring. Lambda strains, mutated at specific sites, are unable to lysogenize cells; instead, they grow and enter the lytic cycle after superinfecting an already lysogenized cell.

<span class="mw-page-title-main">Ribosome</span> Synthesizes proteins in cells

Ribosomes are macromolecular machines, found within all cells, that perform biological protein synthesis. Ribosomes link amino acids together in the order specified by the codons of messenger RNA molecules to form polypeptide chains. Ribosomes consist of two major components: the small and large ribosomal subunits. Each subunit consists of one or more ribosomal RNA molecules and many ribosomal proteins. The ribosomes and associated molecules are also known as the translational apparatus.

<span class="mw-page-title-main">Endospore</span> Protective structure formed by bacteria

An endospore is a dormant, tough, and non-reproductive structure produced by some bacteria in the phylum Bacillota. The name "endospore" is suggestive of a spore or seed-like form, but it is not a true spore. It is a stripped-down, dormant form to which the bacterium can reduce itself. Endospore formation is usually triggered by a lack of nutrients, and usually occurs in gram-positive bacteria. In endospore formation, the bacterium divides within its cell wall, and one side then engulfs the other. Endospores enable bacteria to lie dormant for extended periods, even centuries. There are many reports of spores remaining viable over 10,000 years, and revival of spores millions of years old has been claimed. There is one report of viable spores of Bacillus marismortui in salt crystals approximately 25 million years old. When the environment becomes more favorable, the endospore can reactivate itself into a vegetative state. Most types of bacteria cannot change to the endospore form. Examples of bacterial species that can form endospores include Bacillus cereus, Bacillus anthracis, Bacillus thuringiensis, Clostridium botulinum, and Clostridium tetani. Endospore formation is not found among Archaea.

<span class="mw-page-title-main">Dormancy</span> State of minimized physical activity of an organism

Dormancy is a period in an organism's life cycle when growth, development, and physical activity are temporarily stopped. This minimizes metabolic activity and therefore helps an organism to conserve energy. Dormancy tends to be closely associated with environmental conditions. Organisms can synchronize entry to a dormant phase with their environment through predictive or consequential means. Predictive dormancy occurs when an organism enters a dormant phase before the onset of adverse conditions. For example, photoperiod and decreasing temperature are used by many plants to predict the onset of winter. Consequential dormancy occurs when organisms enter a dormant phase after adverse conditions have arisen. This is commonly found in areas with an unpredictable climate. While very sudden changes in conditions may lead to a high mortality rate among animals relying on consequential dormancy, its use can be advantageous, as organisms remain active longer and are therefore able to make greater use of available resources.

<span class="mw-page-title-main">Translation (biology)</span> Cellular process of protein synthesis

In biology, translation is the process in living cells in which proteins are produced using RNA molecules as templates. The generated protein is a sequence of amino acids. This sequence is determined by the sequence of nucleotides in the RNA. The nucleotides are considered three at a time. Each such triple results in addition of one specific amino acid to the protein being generated. The matching from nucleotide triple to amino acid is called the genetic code. The translation is performed by a large complex of functional RNA and proteins called ribosomes. The entire process is called gene expression.

Virulence is a pathogen's or microorganism's ability to cause damage to a host.

<span class="mw-page-title-main">Exotoxin</span> Toxin from bacteria that destroys or disrupts cells

An exotoxin is a toxin secreted by bacteria. An exotoxin can cause damage to the host by destroying cells or disrupting normal cellular metabolism. They are highly potent and can cause major damage to the host. Exotoxins may be secreted, or, similar to endotoxins, may be released during lysis of the cell. Gram negative pathogens may secrete outer membrane vesicles containing lipopolysaccharide endotoxin and some virulence proteins in the bounding membrane along with some other toxins as intra-vesicular contents, thus adding a previously unforeseen dimension to the well-known eukaryote process of membrane vesicle trafficking, which is quite active at the host–pathogen interface.

Bacterial translation is the process by which messenger RNA is translated into proteins in bacteria.

Eukaryotic translation is the biological process by which messenger RNA is translated into proteins in eukaryotes. It consists of four phases: initiation, elongation, termination, and recapping.

In molecular biology, initiation factors are proteins that bind to the small subunit of the ribosome during the initiation of translation, a part of protein biosynthesis.

<span class="mw-page-title-main">Elongation factor</span> Proteins functioning in translation

Elongation factors are a set of proteins that function at the ribosome, during protein synthesis, to facilitate translational elongation from the formation of the first to the last peptide bond of a growing polypeptide. Most common elongation factors in prokaryotes are EF-Tu, EF-Ts, EF-G. Bacteria and eukaryotes use elongation factors that are largely homologous to each other, but with distinct structures and different research nomenclatures.

<span class="mw-page-title-main">5S ribosomal RNA</span> RNA component of the large subunit of the ribosome

The 5S ribosomal RNA is an approximately 120 nucleotide-long ribosomal RNA molecule with a mass of 40 kDa. It is a structural and functional component of the large subunit of the ribosome in all domains of life, with the exception of mitochondrial ribosomes of fungi and animals. The designation 5S refers to the molecule's sedimentation velocity in an ultracentrifuge, which is measured in Svedberg units (S).

<span class="mw-page-title-main">EF-G</span> Prokaryotic elongation factor

EF-G is a prokaryotic elongation factor involved in mRNA translation. As a GTPase, EF-G catalyzes the movement (translocation) of transfer RNA (tRNA) and messenger RNA (mRNA) through the ribosome.

Eukaryotic translation initiation factor 4 G (eIF4G) is a protein involved in eukaryotic translation initiation and is a component of the eIF4F cap-binding complex. Orthologs of eIF4G have been studied in multiple species, including humans, yeast, and wheat. However, eIF4G is exclusively found in domain Eukarya, and not in domains Bacteria or Archaea, which do not have capped mRNA. As such, eIF4G structure and function may vary between species, although the human EIF4G1 has been the focus of extensive studies.

Translational regulation refers to the control of the levels of protein synthesized from its mRNA. This regulation is vastly important to the cellular response to stressors, growth cues, and differentiation. In comparison to transcriptional regulation, it results in much more immediate cellular adjustment through direct regulation of protein concentration. The corresponding mechanisms are primarily targeted on the control of ribosome recruitment on the initiation codon, but can also involve modulation of peptide elongation, termination of protein synthesis, or ribosome biogenesis. While these general concepts are widely conserved, some of the finer details in this sort of regulation have been proven to differ between prokaryotic and eukaryotic organisms.

<span class="mw-page-title-main">RMF RNA motif</span>

The rmf RNA motif is a conserved RNA structure that was originally detected using bioinformatics. rmf RNAs are consistently foundwithin species classified into the genus Pseudomonas, and is located potentially in the 5′ untranslated regions of rmf genes. These genes encodes the ribosome modulation factor protein, which affects the translation of genes by modifying ribosome structure in response to stress such as starvation. This ribosome modulation is a part of the stringent response in bacteria. The likely biological role of rmf RNAs is ambiguous. Since the RNA could be in the 5′ UTRs of protein-coding genes, it was hypothesized that it functions as a cis-regulatory element. This hypothesis is bolstered by the observation that ribosome modulation factor binds ribosomal RNA, and many cis-regulatory RNAs called ribosomal protein leaders participate in a feedback regulation mechanism by binding to proteins that normally bind to ribosomal RNA. However, since rmf RNAs are not very close to the rmf genes, they might function as non-coding RNAs.

<span class="mw-page-title-main">Bacterial DNA binding protein</span>

In molecular biology, bacterial DNA binding proteins are a family of small, usually basic proteins of about 90 residues that bind DNA and are known as histone-like proteins. Since bacterial binding proteins have a diversity of functions, it has been difficult to develop a common function for all of them. They are commonly referred to as histone-like and have many similar traits with the eukaryotic histone proteins. Eukaryotic histones package DNA to help it to fit in the nucleus, and they are known to be the most conserved proteins in nature. Examples include the HU protein in Escherichia coli, a dimer of closely related alpha and beta chains and in other bacteria can be a dimer of identical chains. HU-type proteins have been found in a variety of bacteria and archaea, and are also encoded in the chloroplast genome of some algae. The integration host factor (IHF), a dimer of closely related chains which is suggested to function in genetic recombination as well as in translational and transcriptional control is found in Enterobacteria and viral proteins including the African swine fever virus protein A104R.

The bacterial stress response enables bacteria to survive adverse and fluctuating conditions in their immediate surroundings. Various bacterial mechanisms recognize different environmental changes and mount an appropriate response. A bacterial cell can react simultaneously to a wide variety of stresses and the various stress response systems interact with each other by a complex of global regulatory networks.

<span class="mw-page-title-main">Universal stress protein</span>

The universal stress protein (USP) domain is a superfamily of conserved genes which can be found in bacteria, archaea, fungi, protozoa and plants. Proteins containing the domain are induced by many environmental stressors such as nutrient starvation, drought, extreme temperatures, high salinity, and the presence of uncouplers, antibiotics and metals.

<span class="mw-page-title-main">Spitz (protein)</span> Protein in Drosophila melanogaster

Spitz is a protein in Drosophila species which is the major activator of their epidermal growth factor receptor (EGFR).

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