Structure and function of 5S rRNA in the ribosome

1995 ◽  
Vol 73 (11-12) ◽  
pp. 869-876 ◽  
Author(s):  
Alexey A. Bogdanov ◽  
Olga A. Dontsova ◽  
Svetlana S. Dokudovskaya ◽  
Inna N. Lavrik
Keyword(s):  
Ribosomal Proteins ◽  
5S Rrna ◽  
23S Rrna ◽  
Order Structure ◽  
Structural Domain ◽  
Experimental Approaches ◽  
Living Organisms ◽  
Almost All ◽  
And Function

5S rRNA is a small RNA molecule that is a component of a ribosome from almost all living organisms. In this review, we discuss the biogenesis of 5S rRNA and its properties as an independent structural domain of a ribosome as well as the current concepts concerning the higher order structure of 5S rRNA in free state and in its complexes with ribosomal proteins and its folding in the ribosome. Special attention is paid to recent experimental approaches that have been useful in 5S rRNA studies. Our own data on topography of 5S rRNA in the ribosomes are discussed in detail. The hypothesis describing the possible functional role of 5S rRNA for ribosome functioning is discussed.Key words: 5S rRNA, ribosomes, 23S rRNA, site-directed chemical cross-linking, RNA folding.

Peptidyl transferase and beyond

1995 ◽  
Vol 73 (11-12) ◽  
pp. 1041-1047 ◽  
Author(s):  
Jacek Wower ◽  
Iwona K. Wower ◽  
Stanislav V. Kirillov ◽  
Kirill V. Rosen ◽  
Robert A. Zimmermann ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
Peptide Bond ◽  
23S Rrna ◽  
Peptide Bond Formation ◽  
Peptidyl Transferase ◽  
Peptidyl Transferase Center ◽  
The Past ◽  
And Function ◽  
Trna Binding

The peptidyl transferase center of the Escherichia coli ribosome encompasses a number of 50S-subunit proteins as well as several specific segments of the 23S rRNA. Although our knowledge of the role that both ribosomal proteins and 23S rRNA play in peptide bond formation has steadily increased, the location, organization, and molecular structure of the peptidyl transferase center remain poorly defined. Over the past 10 years, we have developed a variety of photoaffinity reagents and strategies for investigating the topography of tRNA binding sites on the ribosome. In particular, we have used the photoreactive tRNA probes to delineate ribosomal components in proximity to the 3′ end of tRNA at the A, P, and E sites. In this article, we describe recent experiments from our laboratory which focus on the identification of segments of the 23S rRNA at or near the peptidyl transferase center and on the functional role of L27, the 50S-subunit protein most frequently labeled from the acceptor end of A- and P-site tRNAs. In addition, we discuss how these results contribute to a better understanding of the structure, organization, and function of the peptidyl transferase center.Key words: peptidyl transferase, ribosome, tRNA, photoreactive nucleos/tides, crosslinking.

scholarly journals Ubiquitin and Ubiquitin-Like Proteins and Domains in Ribosome Production and Function: Chance or Necessity?

2021 ◽  
Vol 22 (9) ◽  
pp. 4359
Author(s):  
Sara Martín-Villanueva ◽  
Gabriel Gutiérrez ◽  
Dieter Kressler ◽  
Jesús de la Cruz
Keyword(s):  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Ribosome Assembly ◽  
Cellular Processes ◽  
Substrate Protein ◽  
Precursor Proteins ◽  
Assembly Factors ◽  
Ubiquitin Moiety ◽  
And Function

Ubiquitin is a small protein that is highly conserved throughout eukaryotes. It operates as a reversible post-translational modifier through a process known as ubiquitination, which involves the addition of one or several ubiquitin moieties to a substrate protein. These modifications mark proteins for proteasome-dependent degradation or alter their localization or activity in a variety of cellular processes. In most eukaryotes, ubiquitin is generated by the proteolytic cleavage of precursor proteins in which it is fused either to itself, constituting a polyubiquitin precursor, or as a single N-terminal moiety to ribosomal proteins, which are practically invariably eL40 and eS31. Herein, we summarize the contribution of the ubiquitin moiety within precursors of ribosomal proteins to ribosome biogenesis and function and discuss the biological relevance of having maintained the explicit fusion to eL40 and eS31 during evolution. There are other ubiquitin-like proteins, which also work as post-translational modifiers, among them the small ubiquitin-like modifier (SUMO). Both ubiquitin and SUMO are able to modify ribosome assembly factors and ribosomal proteins to regulate ribosome biogenesis and function. Strikingly, ubiquitin-like domains are also found within two ribosome assembly factors; hence, the functional role of these proteins will also be highlighted.

Pentose Phosphate Pathway in Disease and Therapy

2014 ◽  
Vol 995 ◽  
pp. 1-27 ◽  
Author(s):  
Mahbuba Rahman ◽  
M. Rubayet Hasan
Keyword(s):  
Metabolic Pathways ◽  
Cell Cycle Progression ◽  
Metabolic Diseases ◽  
Pentose Phosphate ◽  
Cycle Progression ◽  
Novel Drugs ◽  
Abnormal Cells ◽  
Living Organisms ◽  
And Function

Pentose phosphate (PP) pathway, which is ubiquitously present in all living organisms, is one of the major metabolic pathways associated with glucose metabolism. The most important functions of this pathway includes the generation of reducing equivalents in the form of NADPH for reductive biosynthesis, and production of ribose sugars for the biosynthesis of nucleotides, amino acids, and other macromolecules required by all living cells. Under normal conditions of growth, PP pathway is important for cell cycle progression, myelin formation, and the maintenance of the structure and function of brain, liver, cortex and other organs. Under diseased conditions, such as in cases of many metabolic, neurological or malignant diseases, pathological mechanisms augment due to defects in the PP pathway genes. Adoption of alternative metabolic pathways by cells that are metabolically abnormal, or malignant cells that are resistant to chemotherapeutic drugs often plays important roles in disease progression and severity. Accordingly, the PP pathway has been suggested to play critical roles in protecting cancer or abnormal cells by providing reduced environment, to protect cells from oxidative damage and generating structural components for nucleic acids biosynthesis. Novel drugs that targets one or more components of the PP pathway could potentially serve to overcome challenges associated with currently available therapeutic options for many metabolic and non-metabolic diseases. However, careful designing of drugs is critical that takes into the accounts of cell’s broader genomic, proteomic and metabolic contexts under consideration, in order to avoid undesirable side-effects. In this review, we discuss the role of PP pathway under normal and abnormal physiological conditions and the potential of the PP pathway as a target for new drug development to treat metabolic and non-metabolic diseases.

scholarly journals Expanding Role of Ubiquitin in Translational Control

2020 ◽  
Vol 21 (3) ◽  
pp. 1151 ◽  
Author(s):  
Shannon E. Dougherty ◽  
Austin O. Maduka ◽  
Toshifumi Inada ◽  
Gustavo M. Silva
Keyword(s):  
Translational Control ◽  
Ribosomal Proteins ◽  
Ribosome Biogenesis ◽  
Rna Binding ◽  
Protein Quality ◽  
Rna Binding Proteins ◽  
Ubiquitin Chain ◽  
Molecular Aspects ◽  
And Function

The eukaryotic proteome has to be precisely regulated at multiple levels of gene expression, from transcription, translation, and degradation of RNA and protein to adjust to several cellular conditions. Particularly at the translational level, regulation is controlled by a variety of RNA binding proteins, translation and associated factors, numerous enzymes, and by post-translational modifications (PTM). Ubiquitination, a prominent PTM discovered as the signal for protein degradation, has newly emerged as a modulator of protein synthesis by controlling several processes in translation. Advances in proteomics and cryo-electron microscopy have identified ubiquitin modifications of several ribosomal proteins and provided numerous insights on how this modification affects ribosome structure and function. The variety of pathways and functions of translation controlled by ubiquitin are determined by the various enzymes involved in ubiquitin conjugation and removal, by the ubiquitin chain type used, by the target sites of ubiquitination, and by the physiologic signals triggering its accumulation. Current research is now elucidating multiple ubiquitin-mediated mechanisms of translational control, including ribosome biogenesis, ribosome degradation, ribosome-associated protein quality control (RQC), and redox control of translation by ubiquitin (RTU). This review discusses the central role of ubiquitin in modulating the dynamism of the cellular proteome and explores the molecular aspects responsible for the expanding puzzle of ubiquitin signals and functions in translation.

scholarly journals Involvement of Various Enzymes in the Physiology and Pathogenesis of Streptococcus suis

2020 ◽  
Vol 7 (4) ◽  
pp. 143
Author(s):  
Chengkun Zheng ◽  
Man Wei ◽  
Mengdie Jia ◽  
ManMan Cao
Keyword(s):  
Streptococcus Suis ◽  
Infection Process ◽  
Swine Industry ◽  
Serine Threonine Kinase ◽  
Future Directions ◽  
Threonine Kinase ◽  
Severe Infections ◽  
Living Organisms ◽  
Almost All

Streptococcus suis causes severe infections in both swine and humans, making it a serious threat to the swine industry and public health. Insight into the physiology and pathogenesis of S. suis undoubtedly contributes to the control of its infection. During the infection process, a wide variety of virulence factors enable S. suis to colonize, invade, and spread in the host, thus causing localized infections and/or systemic diseases. Enzymes catalyze almost all aspects of metabolism in living organisms. Numerous enzymes have been characterized in extensive detail in S. suis, and have shown to be involved in the pathogenesis and/or physiology of this pathogen. In this review, we describe the progress in the study of some representative enzymes in S. suis, such as ATPases, immunoglobulin-degrading enzymes, and eukaryote-like serine/threonine kinase and phosphatase, and we highlight the important role of various enzymes in the physiology and pathogenesis of this pathogen. The controversies about the current understanding of certain enzymes are also discussed here. Additionally, we provide suggestions about future directions in the study of enzymes in S. suis.

scholarly journals Resistance to Linezolid Caused by Modifications at Its Binding Site on the Ribosome

2011 ◽  
Vol 56 (2) ◽  
pp. 603-612 ◽  
Author(s):  
Katherine S. Long ◽  
Birte Vester
Keyword(s):  
Binding Site ◽  
Ribosomal Proteins ◽  
Resistance Mechanism ◽  
Ribosomal Subunit ◽  
Resistance Mechanisms ◽  
Drug Binding ◽  
23S Rrna ◽  
Detailed Knowledge ◽  
Linezolid Resistance ◽  
Almost All

ABSTRACTLinezolid is an oxazolidinone antibiotic in clinical use for the treatment of serious infections of resistant Gram-positive bacteria. It inhibits protein synthesis by binding to the peptidyl transferase center on the ribosome. Almost all known resistance mechanisms involve small alterations to the linezolid binding site, so this review will therefore focus on the various changes that can adversely affect drug binding and confer resistance. High-resolution structures of linezolid bound to the 50S ribosomal subunit show that it binds in a deep cleft that is surrounded by 23S rRNA nucleotides. Mutation of 23S rRNA has for some time been established as a linezolid resistance mechanism. Although ribosomal proteins L3 and L4 are located further away from the bound drug, mutations in specific regions of these proteins are increasingly being associated with linezolid resistance. However, very little evidence has been presented to confirm this. Furthermore, recent findings on the Cfr methyltransferase underscore the modification of 23S rRNA as a highly effective and transferable form of linezolid resistance. On a positive note, detailed knowledge of the linezolid binding site has facilitated the design of a new generation of oxazolidinones that show improved properties against the known resistance mechanisms.

Cellular copper homeostasis: current concepts on its interplay with glutathione homeostasis and its implication in physiology and human diseases

Metallomics ◽  
2017 ◽  
Vol 9 (10) ◽  
pp. 1376-1388 ◽  
Author(s):  
Ashima Bhattacharjee ◽  
Kaustav Chakraborty ◽  
Aditya Shukla
Keyword(s):  
Trace Element ◽  
Copper Homeostasis ◽  
Human Diseases ◽  
Living Organisms ◽  
Cellular Copper ◽  
Almost All ◽  
Glutathione Homeostasis ◽  
Intracellular Copper

Copper is a trace element essential for almost all living organisms, however the level of intracellular copper needs to be tightly regulated. This review explores the existing literature on the role of glutathione in regulating cellular copper homeostasis.

Structure and function of ribosomal RNA

1995 ◽  
Vol 73 (11-12) ◽  
pp. 997-1009 ◽  
Author(s):  
Harry F. Noller ◽  
Rachel Green ◽  
Gabriele Heilek ◽  
Vernita Hoffarth ◽  
Alexander Hüttenhofer ◽  
...  
Keyword(s):  
16S Rrna ◽  
Hydroxyl Radical ◽  
Ribosomal Proteins ◽  
23S Rrna ◽  
Active Population ◽  
30S Subunit ◽  
Radical Cleavage ◽  
The Individual ◽  
And Function

A refined model has been developed for the folding of 16S rRNA in the 30S subunit, based on additional constraints obtained from new experimental approaches. One set of constraints comes from hydroxyl radical footprinting of each of the individual 30S ribosomal proteins, using free Fe2+–EDTA complex. A second approach uses localized hydroxyl radical cleavage from a single Fe2+tethered to unique positions on the surface of single proteins in the 30S subunit. This has been carried out for one position on the surface of protein S4, two on S17, and three on S5. Nucleotides in 16S rRNA that are essential for P-site tRNA binding were identified by a modification interference strategy. Ribosomal subunits were partially inactivated by chemical modification at a low level. Active, partially modified subunits were separated from inactive ones by binding 3′-biotin-derivatized tRNA to the 30S subunits and captured with streptavidin beads. Essential bases are those that are unmodified in the active population but modified in the total population. The four essential bases, G926, 2mG966, G1338, and G1401 are a subset of those that are protected from modification by P-site tRNA. They are all located in the cleft of our 30S subunit model. The rRNA neighborhood of the acceptor end of tRNA was probed by hydroxyl radical probing from Fe2+tethered to the 5′ end of tRNA via an EDTA linker. Cleavage was detected in domains IV, V, and VI of 23S rRNA, but not in 5S or 16S rRNA. The sites were all found to be near bases that were protected from modification by the CCA end of tRNA in earlier experiments, except for a set of E-site cleavages in domain IV and a set of A-site cleavages in the α-sarcin loop of domain VI. In vitro genetics was used to demonstrate a base-pairing interaction between tRNA and 23S rRNA. Mutations were introduced at positions C74 and C75 of tRNA and positions 2252 and 2253 of 23S rRNA. Interaction of the CCA end of tRNA with mutant ribosomes was tested using chemical probing in conjunction with allele-specific primer extension. The interaction occurred only when there was a Watson–Crick pairing relationship between positions 74 of tRNA and 2252 of 23S rRNA. Using a novel chimeric in vitro reconstitution method, it was shown that the peptidyl transferase reaction depends on this same Watson–Crick base pair.Key words: rRNA, ribosome, tRNA, hydroxyl radical, ribosomal protein.

scholarly journals Metallothioneins: Diverse Protein Family to Bind Metallic Ions

2021 ◽  
Author(s):  
Ettiyagounder Parameswari ◽  
Tamilselvan Ilakiya ◽  
Veeraswamy Davamani ◽  
Periasami Kalaiselvi ◽  
Selvaraj Paul Sebastian
Keyword(s):  
Metal Ions ◽  
Growth Regulation ◽  
Class I ◽  
Reduced Form ◽  
Metallic Ions ◽  
Class Iii ◽  
Structure Conservation ◽  
Living Organisms ◽  
Almost All ◽  
And Function

Metallothionein’s (MTs) are the lower molecular weight (6-7 kDa) proteins that are found to be present in almost all organism types ranging from prokaryotes to eukaryotes species. MT are the metal detecting proteins that can mitigate the effect caused by the excess metal ions. They are also found to be involved in cellular process such as cell growth regulation, ROS (Reactive Oxygen Species) and DNA repair. The protein was termed as Metallothionein due to the unusual higher metal (metallo) and the sulfur (thiol) content. They are further grouped into 3 classes viz., class I, II and III. The Class I and II MTs are polypeptides that were obtained from direct gene products, the class III MTs are from the cysteine-rich non-translational molecules that are termed as phytochelatins. The metal ions are been sequestered through the MTs with Cys rich motifs. All the cysteines are present in the reduced form and are been co-ordinated through the mercaptide bonds. The cysteines present in the MTs are preserved across the species, it is supposed that, cysteines are essential for the function and the MTs are required for the life. Metallothionins structure, conservation in evolution, their ubiquitous nature of occurrence, the genes redundancy and the programmed MTs synthesis in development, regeneration and reproduction of living organisms are some of the weighty arguments in suspecting MTs to also serve others and perhaps the high particular metal-related cellular roles. In this chapter, there is a detailed discussion about Metallothionein its structure, occurrence and function.

scholarly journals CNBP controls transcription by unfolding DNA G-quadruplex structures

2019 ◽  
Vol 47 (15) ◽  
pp. 7901-7913 ◽  
Author(s):  
Aldana P David ◽  
Angélique Pipier ◽  
Federico Pascutti ◽  
Andrés Binolfi ◽  
Andrea M J Weiner ◽  
...  
Keyword(s):  
Transcriptional Control ◽  
Regulatory Elements ◽  
Transcription Start Sites ◽  
G4 Dna ◽  
Dna Strands ◽  
Living Organisms ◽  
And Function

Abstract Guanine-rich DNA strands can fold into non-canonical four-stranded secondary structures named G-quadruplexes (G4). Experimental evidences suggest that G4-DNA surrounding transcription start sites act as cis-regulatory elements by either stimulating or inhibiting gene transcription. Therefore, proteins able to target and regulate specific G4 formation/unfolding are crucial for G4-mediated transcriptional control. Here we present data revealing that CNBP acts in vitro as a G4-unfolding protein over a tetramolecular G4 formed by the TG4T oligonucleotide, as well as over the G4 folded in the promoters of several oncogenes. CNBP depletion in cellulo led to a reduction in the transcription of endogenous KRAS, suggesting a regulatory role of CNBP in relieving the transcriptional abrogation due to G4 formation. CNBP activity was also assayed over the evolutionary conserved G4 enhancing the transcription of NOGGIN (NOG) developmental gene. CNBP unfolded in vitro NOG G4 and experiments performed in cellulo and in vivo in developing zebrafish showed a repressive role of CNBP on the transcription of this gene by G4 unwinding. Our results shed light on the mechanisms underlying CNBP way of action, as well as reinforce the notion about the existence and function of G4s in whole living organisms.

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