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Methods of Increasing Translational Fidelity[edit]
Amino Acid Activation[edit]
The linking of an amino acid to a tRNA has two functions and the enzyme responsible for this reaction is aminoacyl-tRNA synthase[1]. The first step in amino acid activation is to provide the tRNA the energy required for transpeptidation[1]. The amino acid is activated by ATP, which results in the formation of an amino acid adenylate[1]. The second step is charging the tRNA with the correct amino acid adenylate and this step mediated by a proofreading mechanism known as the double-sieve model[2].
Double-Sieve Model[edit]
The double-sieve model eliminates the probability misacylation of amino acids by using a catalytic and hydrolytic domain[2]. An amino acid larger than the one that matches the tRNA is rarely activated because it will be to large to fit into active site of the aminoacyl-tRNA synthetase (first sieving)[2]. Once the amino acid passes the first sieve it will be charged onto the tRNA and then the hydrolytic site of the same synthetase will act as the second sieve[2]. The hydrolytic site will be too small for the correct amino acid (second sieving) to pass through[2]. Therefore an incorrect amino acid will pass through the second sieve and it will be eliminated by hydrolysis, while only the correct amino acid which cannot pass through the second sieve will remain charged and be used for translation[2].
EF-Tu-GTP[edit]
A protein complex called EF-Tu-GTP is responsible for transporting aminoacyl-tRNAs to the ribosome by covalently binding to the aminoacyl-tRNA[4]. The aminoacyl-tRNA-EF-Tu-GTP complex will bind to the ribosome[4]. If the A site of the ribosome accepts the aminoacyl-tRNA that is selected, a GTPase will hydrolyze the GTP bound to aminoacyl-tRNA-EF-Tu-GTP[4]. Hydrolization of the GTP molecule results in a conformational change on the aminoacyl-tRNA-EF-Tu-GDP complex[4]. The conformation change also produces stress on the codon and anti-codon interaction between the aminoacyl-tRNA-EF-Tu-GDP complex and the ribosome[4]. If codon and anti-codon interaction is not the correct match then the aminoacyl-tRNA-EF-Tu-GDP complex will be released[4]. However if the codon and anti-codon interaction matches then only the EF-Tu-GDP complex will be released[4].
Accommodation[edit]
After the release of the Aminoacyl-tRNA by EF-Tu-GDP, the amino-acid attached to the Aminoacyl-tRNA is not oriented in the correct position for transpeptidation[6]. The aminoacyl-tRNA must undergo accommodation for the amino-acid to be oriented towards the P site of the ribosome near the extending polypeptide[6]. If the codon and anti-codon interaction is not perfect during the accommodation step, the Aminoacyl-tRNA will not be able to withstand the stress of the accommodation and is released[6].
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- ^ a b c Berg, Jeremy M.; Tymoczko, John L.; Stryer, Lubert (2002-01-01). "Aminoacyl-Transfer RNA Synthetases Read the Genetic Code".
{{cite journal}}: Cite journal requires|journal=(help) - ^ a b c d e f Moras, Dino (2010-12-21). "Proofreading in translation: Dynamics of the double-sieve model". Proceedings of the National Academy of Sciences. 107 (51): 21949–21950. doi:10.1073/pnas.1016083107. ISSN 0027-8424. PMC 3009764. PMID 21149735.
- ^ Garrett, Reginald (2012). Biochemistry. Nelson College Indigenous. ISBN 0176502653.
- ^ a b c d e f g Ogle, James M.; Ramakrishnan, V. "STRUCTURAL INSIGHTS INTO TRANSLATIONAL FIDELITY". Annual Review of Biochemistry. 74 (1): 129–177. doi:10.1146/annurev.biochem.74.061903.155440.
- ^ Ogle, James M.; Ramakrishnan, V. (2005-01-01). "Structural Insights into Translational Fidelity". Annual Review of Biochemistry. 74 (1): 129–177. doi:10.1146/annurev.biochem.74.061903.155440. PMID 15952884.
- ^ a b c "Insights into the decoding mechanism from recent ribosome structures". Trends in biochemical sciences. May 2003.