- Aminoacyl-tRNAsynthetases are very specific for amino-acylation of tRNAs with the correct cognate amino acids. However, there is a possibility of a mismatch between the tRNA and its cognate amino acid. This error is corrected by the inherent proof reading activity of the aminoacyl-tRNA, synthetase. In case of two very similar amino acids, namely valine and isoleucine, isoleucyl-tRNAsynthetase employs the following possible approaches for an error free amino acylation
A. It removes an incorrect amino acid by hydrolyzing the aminoacyl-AMP linkage following first reaction
B. It is activated for proof-reading activity, leading to breakage of the bond between the wrong amino acid and tRNA.
C. It has an intrinsic ability to recognize the structural difference between amino acids leading to abortive elimination of the non-cognate amino acid.
D. It getssequestered in the second step with the wrong amino acid, and that freezes the amino acylation process.
Which of the following combinations is correct
(1) A and B (2) A and D
(3) B and D(4) C and DProofreading Mechanisms of Isoleucyl-tRNA Synthetase (IleRS) for Accurate Aminoacylation
Aminoacyl-tRNA synthetases (aaRSs) are critical enzymes that attach the correct amino acid to their cognate tRNA, ensuring fidelity in protein synthesis. Isoleucyl-tRNA synthetase (IleRS) faces a particular challenge in discriminating between isoleucine and structurally similar amino acids like valine. To maintain accuracy, IleRS employs sophisticated proofreading mechanisms.
Understanding the Proofreading Approaches of IleRS
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Pre-transfer editing (A):
IleRS can hydrolyze the aminoacyl-AMP intermediate if the wrong amino acid is activated, preventing its transfer to tRNA. This step removes incorrect amino acids early in the reaction cycle. -
Post-transfer editing (B):
After the amino acid is transferred to tRNA, IleRS can hydrolyze the bond between the incorrect amino acid and the tRNA, releasing the misacylated tRNA and preventing mistranslation. -
Structural discrimination (C):
IleRS has an intrinsic ability to recognize subtle structural differences between amino acids, but this alone is insufficient to prevent all errors, hence the need for editing. -
Sequestration (D):
The enzyme does not freeze the aminoacylation process upon binding the wrong amino acid; instead, it actively edits or removes the mischarged amino acid.
Evaluating the Statements
Statement Description Correctness A Hydrolyzes aminoacyl-AMP linkage to remove incorrect amino acid (pre-transfer editing) Correct B Breaks bond between wrong amino acid and tRNA (post-transfer editing) Correct C Recognizes structural differences leading to abortive elimination Partially true but not the main proofreading mechanism D Sequestration freezes aminoacylation process Incorrect
Correct Combinations
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The proofreading activity of IleRS mainly involves pre-transfer editing (A) and post-transfer editing (B).
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Sequestration (D) is not a proofreading mechanism.
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Structural recognition (C) assists but is not sufficient alone for error-free aminoacylation.
Correct Answer
(1) A and B
Keywords for SEO Optimization
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Isoleucyl-tRNA synthetase proofreading
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Pre-transfer and post-transfer editing
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Aminoacyl-tRNA synthetase fidelity
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Valine and isoleucine discrimination
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Aminoacyl-AMP hydrolysis
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Protein synthesis accuracy
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Kinetic proofreading mechanisms
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Editing domain of IleRS
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Translation error correction
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Molecular basis of amino acid selection
Conclusion
Isoleucyl-tRNA synthetase employs a double-layered proofreading strategy to ensure high fidelity in aminoacylation. It hydrolyzes incorrect aminoacyl-AMP intermediates (pre-transfer editing) and breaks the bond between misacylated tRNA and wrong amino acids (post-transfer editing). These mechanisms together maintain translation accuracy, especially when distinguishing between chemically similar amino acids like valine and isoleucine.
Correct answer: (1) A and B
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