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Biochemistry. Biokhimiia Aug 2013Translation, that is biosynthesis of polypeptides in accordance with information encoded in the genome, is one of the most important processes in the living cell, and it... (Review)
Review
Translation, that is biosynthesis of polypeptides in accordance with information encoded in the genome, is one of the most important processes in the living cell, and it has been in the spotlight of international research for many years. The mechanisms of protein biosynthesis in bacteria and in the eukaryotic cytoplasm are now understood in great detail. However, significantly less is known about translation in eukaryotic mitochondria, which is characterized by a number of unusual features. In this review, we summarize current knowledge about mitochondrial translation in different organisms while paying special attention to the aspects of this process that differ from cytoplasmic protein biosynthesis.
Topics: Animals; Humans; Mitochondria; Mitochondrial Proteins; Peptide Chain Elongation, Translational; Peptide Chain Initiation, Translational; Peptide Chain Termination, Translational; RNA
PubMed: 24228873
DOI: 10.1134/S0006297913080014 -
Cold Spring Harbor Perspectives in... Dec 2018This review summarizes our current understanding of the major pathway for the initiation phase of protein synthesis in eukaryotic cells, with a focus on recent advances.... (Review)
Review
This review summarizes our current understanding of the major pathway for the initiation phase of protein synthesis in eukaryotic cells, with a focus on recent advances. We describe the major scanning or messenger RNA (mRNA) mG cap-dependent mechanism, which is a highly coordinated and stepwise regulated process that requires the combined action of at least 12 distinct translation factors with initiator transfer RNA (tRNA), ribosomes, and mRNAs. We limit our review to studies involving either mammalian or budding yeast cells and factors, as these represent the two best-studied experimental systems, and only include a reference to other organisms where particular insight has been gained. We close with a brief description of what we feel are some of the major unknowns in eukaryotic initiation.
Topics: Animals; Eukaryotic Cells; Peptide Chain Initiation, Translational; Protein Biosynthesis
PubMed: 29735639
DOI: 10.1101/cshperspect.a033092 -
Topics in Current Chemistry 2013Chirality is present at all levels of structural hierarchy of protein and plays a significant role in protein biosynthesis. The macromolecules involved in protein... (Review)
Review
Chirality is present at all levels of structural hierarchy of protein and plays a significant role in protein biosynthesis. The macromolecules involved in protein biosynthesis such as aminoacyl tRNA synthetase and ribosome have chiral subunits. Despite the omnipresence of chirality in the biosynthetic pathway, its origin, role in current pathway, and importance is far from understood. In this review we first present an introduction to biochirality and its relevance to protein biosynthesis. Major propositions about the prebiotic origin of biomolecules are presented with particular reference to proteins and nucleic acids. The problem of the origin of homochirality is unresolved at present. The chiral discrimination by enzymes involved in protein synthesis is essential for keeping the life process going. However, questions remained pertaining to the mechanism of chiral discrimination and concomitant retention of biochirality. We discuss the experimental evidence which shows that it is virtually impossible to incorporate D-amino acids in protein structures in present biosynthetic pathways via any of the two major steps of protein synthesis, namely aminoacylation and peptide bond formation reactions. Molecular level explanations of the stringent chiral specificity in each step are extended based on computational analysis. A detailed account of the current state of understanding of the mechanism of chiral discrimination during aminoacylation in the active site of aminoacyl tRNA synthetase and peptide bond formation in ribosomal peptidyl transferase center is presented. Finally, it is pointed out that the understanding of the mechanism of retention of enantiopurity has implications in developing novel enzyme mimetic systems and biocatalysts and might be useful in chiral drug design.
Topics: Evolution, Molecular; Protein Biosynthesis; Stereoisomerism
PubMed: 23019095
DOI: 10.1007/128_2012_369 -
The Journal of General Physiology Jul 1966Outline of the steps in protein synthesis. Nature of the genetic code. The use of synthetic oligo- and polynucleotides in deciphering the code. Structure of the code:... (Review)
Review
Outline of the steps in protein synthesis. Nature of the genetic code. The use of synthetic oligo- and polynucleotides in deciphering the code. Structure of the code: relatedness of synonym codons. The wobble hypothesis. Chain initiation and N-formyl-methionine. Chain termination and nonsense codons. Mistakes in translation: ambiguity in vitro. Suppressor mutations resulting in ambiguity. Limitations in the universality of the code. Attempts to determine the particular codons used by a species. Mechanisms of suppression, caused by (a) abnormal aminoacyl-tRNA, (b) ribosomal malfunction. Effect of streptomycin. The problem of "reading" a nucleic acid template. Different ribosomal mutants and DNA polymerase mutants might cause different mistakes. The possibility of involvement of allosteric proteins in template reading.
Topics: Genetic Code; Protein Biosynthesis
PubMed: 5338560
DOI: 10.1085/jgp.49.6.305 -
British Medical Bulletin Sep 1965
Review
Topics: In Vitro Techniques; Protein Biosynthesis
PubMed: 5317920
DOI: 10.1093/oxfordjournals.bmb.a070399 -
Annual Review of Biochemistry 1960
Topics: Protein Biosynthesis; Proteins
PubMed: 13810951
DOI: 10.1146/annurev.bi.29.070160.002521 -
Annual Review of Biochemistry 1959
Topics: Protein Biosynthesis; Proteins
PubMed: 14446852
DOI: 10.1146/annurev.bi.28.070159.001045 -
Annual Review of Biochemistry 1962
Topics: Protein Biosynthesis; Proteins
PubMed: 13913227
DOI: 10.1146/annurev.bi.31.070162.002001 -
Current Opinion in Clinical Nutrition... Jan 2007Protein synthesis and degradation govern protein turnover, which underlies the adaptation of organisms to changing developmental, physiological and environmental needs.... (Review)
Review
PURPOSE OF REVIEW
Protein synthesis and degradation govern protein turnover, which underlies the adaptation of organisms to changing developmental, physiological and environmental needs. The cellular mechanisms of these processes have been increasingly uncovered. Recent findings establishing additional links between protein synthesis and degradation are the topic of this review.
RECENT FINDINGS
Several major developments in the field have taken place recently. First, the role of lysosomal-autophagosomal degradation, the established amino acid supplier for protein synthesis, has been demonstrated for additional diverse aspects of cellular physiology. Second, cytosolic protein degradation initiated by the proteasome has been assigned a critical role in sustaining ongoing protein synthesis upon acute nutrient restriction. A number of regulatory possibilities to modulate the intracellular amino acid flux by means of proteasomal degradation are discussed. Finally, the field of translation factor regulation by their degradation has emerged recently and is described here.
SUMMARY
The elucidation of mechanisms determining protein turnover and, thus, cellular adaptation will help us to understand the (patho)physiological conditions caused or accompanying acute and chronic nutrient deficiencies and should lead to new therapeutic strategies to handle them.
Topics: Adaptation, Physiological; Amino Acids; Humans; Proteasome Endopeptidase Complex; Protein Biosynthesis; Ubiquitin
PubMed: 17143051
DOI: 10.1097/MCO.0b013e328011645b -
Cold Spring Harbor Perspectives in... Sep 2018This review summarizes our current understanding of translation in prokaryotes, focusing on the mechanistic and structural aspects of each phase of translation:... (Review)
Review
This review summarizes our current understanding of translation in prokaryotes, focusing on the mechanistic and structural aspects of each phase of translation: initiation, elongation, termination, and ribosome recycling. The assembly of the initiation complex provides multiple checkpoints for messenger RNA (mRNA) and start-site selection. Correct codon-anticodon interaction during the decoding phase of elongation results in major conformational changes of the small ribosomal subunit and shapes the reaction pathway of guanosine triphosphate (GTP) hydrolysis. The ribosome orchestrates proton transfer during peptide bond formation, but requires the help of elongation factor P (EF-P) when two or more consecutive Pro residues are to be incorporated. Understanding the choreography of transfer RNA (tRNA) and mRNA movements during translocation helps to place the available structures of translocation intermediates onto the time axis of the reaction pathway. The nascent protein begins to fold cotranslationally, in the constrained space of the polypeptide exit tunnel of the ribosome. When a stop codon is reached at the end of the coding sequence, the ribosome, assisted by termination factors, hydrolyzes the ester bond of the peptidyl-tRNA, thereby releasing the nascent protein. Following termination, the ribosome is dissociated into subunits and recycled into another round of initiation. At each step of translation, the ribosome undergoes dynamic fluctuations between different conformation states. The aim of this article is to show the link between ribosome structure, dynamics, and function.
Topics: Archaea; Bacteria; Gene Expression Regulation, Archaeal; Gene Expression Regulation, Bacterial; Prokaryotic Cells; Protein Biosynthesis
PubMed: 29661790
DOI: 10.1101/cshperspect.a032664