Protein Synthesis Steps Protein Synthesis Steps In Brief
The process of protein synthesis translates the codons (nucleotide triplets) of the messenger RNA (mRNA) into the 20-symbol code of amino acids that build the polypeptide chain of the proteins. The process of mRNA translation begins from its 5?-end towards its 3?-end as the polypeptide chain is synthesized from its amino-terminal (N-end) to its carboxyl-terminal (C-end). There are almost no significant differences in the protein synthesis steps in prokaryotes and eukaryotes, however there is one major distinction between the structure of the mRNAs â€“ prokaryotes often have several coding regions (polycistronic mRNA), while the eukaryotic mRNA has only one coding region (monocistronic mRNA). The main protein synthesis steps are: Initiation Elongation Termination In most of the aspects, the process in eukaryotes follow the same simple protein synthesis steps as in prokaryotes. However there are specific differences that could be outlined. For example, one important difference is that in prokaryotic cells the process of translation starts before transcription is completed. This coupling is defined because prokaryotes have no nuclear membrane and thus there is no physical separation of the two processes.
Protein Synthesis Initiation
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The first of protein synthesis steps is initiation that cover the assembly of the translation system components and precedes the formation of peptide bonds. The components involved in the first step of protein synthesis are:
the mRNA to be translated the two ribosomal subunits (small and large subunits) the aminoacyl-tRNA which is specified by the first codon in the mRNA guanosine triphosphate (GTP), which provides energy for the process – eukaryotes require also adenosine triphosphate! initiation factors which enables the assembly of this initiation complex – prokaryotes have 3 initiation factors are known (IF-1, IF-2, and IF-3), while eukaryotes, there have over ten factors designated with eIF prefix. Two mechanisms are involved in the recognition of nucleotide sequence (AUG) by the ribosome, which actually initiates translation: 1. Shine-Dalgarno (SD) sequence – In Escherichia coli is observed sequence with high percentage of purine nucleotide bases, known as the Shine-Dalgarno sequence. This region is located close to 5’ end of the mRNA molecule, 6-10 bases upstream of the initiating codon. The 16S rRNA component of the small ribosomal subunit possess a complementary to the SD sequence near its 3?-end. Thus the two complementary sequences can couple, which facilitates the positioning of the 30S ribosomal subunit on the mRNA in proximity to the initiation codon. The mechanism is slightly different in eukaryotes because they do not have SD sequences. In eukaryotes, with the assistance of the eIF-4 initiation factors, the 40S ribosomal subunit binds close to a structure called “cap structure” at the 5-end of the mRNA and then moves down the messenger RNA sequence till it finds the initiating codon. However this process requires energy from ATP. 2. Initiating codon (AUG) – The initiating AUG triplet is recognized by a special initiator tRNA. In prokaryotes this event is facilitated by IF-2-GTP, while in eukaryotes by eIF-2-GTP and additional eIFs. The charged initiator transport RNA aproaches the P
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site on the small ribosomal subunit. In bacteria (and in mitochondria), a methionine is attached to the initiator tRNA an subsequently a formyl group is added by the enzyme transformylase, which uses N10-formyl tetrahydrofolate as the carbon donor â€“ finally a N-formylated methionine is attached to the initiator tRNA. For comparison, in eukaryotes, the initiator transport RNA attaches a non formylated methionine. In both types of cells, this N-terminal methionine attached to the 5â€™-end is removed before the end of the translation. In the last step of the initiation, the large ribosomal subunit joins the complex formed by now, and thus a fully functional ribosome is formed. This complex has a charged initiating tRNA in the P site, and the A site empty. During this protein synthesis step is used the energy within the GTP on (e)IF-2, which gets hydrolyzed to GDP. The reactivation of (e)IF-2-GDP is facilitated by A guanine nucleotide exchange factor.
Translation elongation is second in protein synthesis steps. During the elongation step the polypeptide chain adds amino acids to the carboxyl end the chain protein grows as the ribosome moves from the 5? -end to the 3?-end of the mRNA. In prokaryotes, the delivery of the aminoacyl-tRNA to ribosomal A site is facilitated by elongation factors EF-Tu-GTP and EF-Ts, and requires GTP hydrolysis. In eukaryotes, the analogous elongation factors are EF-1??GTP and EF-1??. Both EF-Ts (in prokatyotes) and EF-1?? (in eukaryotes) function as nucleotide exchange factors. The peptidyl-transferase is an important enzyme which catalyzes the formation of the peptide bonds. The enzymatic activity is found to be intrinsic to the 23S rRNA found in the large ribosomal subunit. Because this rRNA catalyzes the polypeptide bound formation reaction, it is named as a ribozyme. The transport RNA at the P site carries the polypeptide synthesized by now, while on the A site is located a tRNA, which is bound to a single amino acid. After the peptide bond has been
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formed between the polypeptide and the amino acid, the newly formed polypeptide is linked to the tRNA at the A site. Once this step is completed, the ribosome moves 3 nucleotides toward the 3?-end of the mRNA. This process is known as translocation – in prokaryotes, it requires the participation of EF-G-GTP and GTP hydrolysis, while the eukaryotic cells use EF-2-GTP and GTP hydrolysis again. During the translocation, the uncharged tRNA moves from the P to the E site and peptidyl-tRNA leaves the A site and go to the P site. This is an iterative process that is repeated until the ribosome reaches the termination codon.
Termination of Translation
Termination happens when the A site of the ribosome reaches one of the three termination codons (UAA, UAG or UGA). In prokaryotes, these codons are recognized by different release factors (abbreviated with RF). RF-1 is responsible for the recognition of termination codons UAA and UAG, while RF-2 – UGA and UAA. When these release factors bind the complex, this cause in hydrolysis of the bond linking the peptide to the tRNA at the P site and releases the nascent protein from the ribosome. Then a third release factor (RF-3-GTP) causes the release of RF-1 or RF-2 as GTP is hydrolyzed to GDP and single phosphate reqidue. In contrast, the eukaryote cells have just one release factor, eRF, which can recognize all three termination codons. A second factor is involved – eRF-3, with a similar function to the RF-3 in prokaryote cells. The protein synthesis steps in prokaryotes are summarized in figure below.
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Some antibiotic inhibitors that could be involved at different protein synthesis steps are: diphtheria toxin, which inactivates EF-2 and thus prevents the translocation clindamycin and erythromycin, which blocks (due to irreversible binding) to a site within the 50S sub-unit of the ribosome and in this way inhibit the translocation ricin (from castor beans) is a very potent toxin that exerts its effects by removing an adenine from 28S rRNA, thus inhibiting the function of eukaryotic ribosomes.
Topics Related To Protein Synthesis Steps Formation of Polysomes Protein targeting Regulation of Translation
Protein Synthesis Steps Described With Images
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Latest Resarch Articles For Protein Synthesis Steps – Initiation, Elongation and Termination Termination of protein synthesis in mammalian mitochondria. Related Articles Termination of protein synthesis in mammalian mitochondria. J Biol Chem. 2011 Oct 7;286(40):34479-85 Authors: Chrzanowska-Lightowlers ZM, Pajak A, Lightowlers RN Abstract All mechanisms of protein synthesis can be considered in four stages: initiation, elongation, termination, and ribosome recycling. Remarkable progress has been made in unde […] Exercise, amino acids, and aging in the control of human muscle protein synthesis. Related Articles Exercise, amino acids, and aging in the control of human muscle protein synthesis. Med Sci Sports Exerc. 2011 Dec;43(12):2249-58 Authors: Walker DK, Dickinson JM, Timmerman KL, Drummond MJ, Reidy PT, Fry CS, Gundermann DM, Rasmussen BB Abstract In this review, we discuss recent research in the field of human skeletal muscle protein metabolis […] Triennial Growth Symposium: leucine acts as a nutrient signal to stimulate protein synthesis in neonatal pigs. Related Articles Triennial Growth Symposium: leucine acts as a nutrient signal to stimulate protein synthesis in neonatal pigs. J Anim Sci. 2011 Jul;89(7):2004-16 Authors: Suryawan A, Orellana RA, Fiorotto ML, Davis TA Abstract The postprandial increases in AA and insulin independently stimulate protein synthesis in skeletal muscle of piglets. Leucine is an […] Regulation of protein synthesis and the role of eIF3 in cancer. Related Articles Regulation of protein synthesis and the role of eIF3 in cancer. Braz J Med Biol Res. 2010 Oct;43(10):920-30 Authors: Hershey JW Abstract Maintenance of cell homeostasis and regulation of cell proliferation depend importantly on regulating the process of protein synthesis. Many disease states arise when disregulation of protein synthesis occu […] Terminating human mitochondrial protein synthesis: a shift in our thinking. Related Articles Terminating human mitochondrial protein synthesis: a shift in our thinking. RNA Biol. 2010 May-Jun;7(3):282-6 Authors: Lightowlers RN, Chrzanowska-Lightowlers ZM Abstract Until recently, human mitochondria were regarded as unusual as they appeared to employ four stop codons to terminate translation. In addition to the UAA/UAG of the universa […] The role of Myc-induced protein synthesis in cancer. Related Articles The role of Myc-induced protein synthesis in cancer. Cancer Res. 2009 Dec 1;69(23):8839-43 Authors: Ruggero D Abstract Deregulation in different steps of translational control is an emerging mechanism for cancer formation. One example of an
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oncogene with a direct role in control of translation is the Myc transcription factor. Myc directly in […] The role of protein synthesis in cell cycling and cancer. Related Articles The role of protein synthesis in cell cycling and cancer. Mol Oncol. 2009 Dec;3(5-6):402-8 Authors: White-Gilbertson S, Kurtz DT, Voelkel-Johnson C Abstract Cell cycling and protein synthesis are both key physiological tasks for cancer cells. Here we present a model for how the elongation phase of protein synthesis, governed by elongation fa […] Acute and chronic ethanol consumption differentially impact pathways limiting hepatic protein synthesis. Related Articles Acute and chronic ethanol consumption differentially impact pathways limiting hepatic protein synthesis. Am J Physiol Endocrinol Metab. 2008 Jul;295(1):E3-9 Authors: Karinch AM, Martin JH, Vary TC Abstract This review identifies the various pathways responsible for modulating hepatic protein synthesis following acute and chronic alcohol into […] A new view of protein synthesis: mapping the free energy landscape of the ribosome using single-molecule FRET. Related Articles A new view of protein synthesis: mapping the free energy landscape of the ribosome using single-molecule FRET. Biopolymers. 2008 Jul;89(7):565-77 Authors: Munro JB, Vaiana A, Sanbonmatsu KY, Blanchard SC Abstract This article reviews the application of single-molecule fluorescence resonance energy transfer (smFRET) methods to the study of pr […] Protein synthesis inhibition and memory: formation vs amnesia. Related Articles Protein synthesis inhibition and memory: formation vs amnesia. Neurobiol Learn Mem. 2008 Mar;89(3):201-11 Authors: Gold PE Abstract Studies using protein synthesis inhibitors have provided key support for the prevalent view that memory formation requires the initiation of protein synthesis as a primary element of the molecular biology of mem […]
Protein Synthesis Steps
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Published on Jun 16, 2013