tRNA Function: Synthetases

• Each tRNA is charged with the proper amino acid via a covalent ester bond at its 3' end by a family of enzymes called aminoacyl-tRNA synthetases.  Each enzyme must recognize both the tRNA(s) specific for an amino acid and the corresponding amino acid.  This energy-consuming process is ATP-dependent and results in the cleavage of two high-energy phosphate bonds (one in going from ATP to AMP + PP, and one for the cleavage of pyrophosphate into two inorganic phosphates:

• There are 20 different aminoacyl-tRNA synthetases, one for each amino acid.  Despite the fact that they all carry out very similar tasks, they vary greatly in size (40-100 kDalton).
• Since there are 61 amino acid codons, most tRNA synthetases must be able to recognize more than one type of tRNA (i.e. 6 codons for Arg).  These tRNAs are called cognate tRNAs for that particular synthetase.  This mapping is achieved through so-called recognition domains on the tRNA.  In the figures below (a result using x-ray crystallopraphy - yeah!), tRNA is shown with a red backbone and yellow bases;  tRNA synthetase is shown as a space-filling model in blue:

• The recognition domains include unique sections of the acceptor stem, loops and/or the anticodon (black dots):

• The accuracy of charging tRNA with the proper amino acid is crucial because once charged, only the tRNA anticodon determines incorporation, not the attached amino acid.

• The error rate of charging is very low:  1 error in 10,000 charging reactions.  This is achieved by two means:

• the amino acid specificity pocket in a specific synthetase will only bind amino acids similar in size and charge.
• the synthetase also has proofreading capability which, once a wrong aminoacyl-adenylate complex is formed (1st step), will hydrolyze the complex before it can be covalently attached to the tRNA (2nd step).

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