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How aminoacyl-tRNA synthetases translate the genetic code
A selection of talks on Biochemistry
The ERK1/2 MAPK cascade
- Prof. Melanie H. Cobb
- University of Texas Southwestern Medical Center at Dallas, USA
Amino acid conjugation: mechanism and enzymology
- Dr. Kathleen Knights
- Flinders University, Australia
How aminoacyl-tRNA synthetases translate the genetic code.
Protein synthesis requires a continual supply of aminoacylated tRNAs. These are used by the ribosome to synthesise the polypeptide chain corresponding to the sequence of nucleotide triplets on the messenger RNA. This process actually involves a two-step decoding of the genetic code, and both steps have to be highly accurate in order to guarantee the fidelity of protein synthesis. First of all enzymes known as aminoacyl-tRNA synthetases ensure the correct identification of an amino acid with its corresponding tRNA anticodon triplet. Synthetases do this by covalently attaching the amino acid to the 3' end of its cognate tRNA, a process known as aminoacylation. The second step is ensuring that the tRNA anticodon is correctly paired with the codon on the mRNA, this is the job of the ribosome using a mechanism described in another talk in this series. The ribosome does not check the identity of the amino acid attached to a tRNA, so if a synthetase charges a tRNA with a wrong amino acid, this can immediately lead to an error in protein sequence. The overall error rate in protein synthesis is about 1:10,000 amino acids.
The synthetases aminoacylate tRNA in a two-step chemical reaction, both steps of which occur in the same active site on the enzyme. Firstly, the amino acid is activated using ATP to form an intermediate called the aminoacyl-adenylate, this remains tightly bound to the enzyme while pyrophosphate is released. In the second step, the ribose of the terminal adenosine at the 3' end of the tRNA is charged with the amino acid, at either the 2' or 3'-hydroxyl, with the concomitant formation of AMP. The aminoacylated tRNA can then leave the enzyme and is subsequently escorted to the ribosome by elongation factor Ef-Tu, to be used in protein synthesis.