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 Aminoacyl tRNA synthetase face two important challenges, 
i. they must recognize the correct set of tRNA for a particular amino acid
ii. they must charge all these iso-accepting tRNAs with the correct amino acid,
Both these processes are carried out with high fidelity by the possible Mechanism:
A. The discrimination ability resides predominantly at the acceptor stem of tRNAs
B. The specificity is contributed by anticodon loop in tRNA
C. The specificity is embedded in the aminoacyl synthetase at the "N" terminus
D. The specificity caused by the variable loop of tRNA
Which of the following combinations is correct?
  • a)
    A and B
  • b)
    B and C
  • c)
    A and C
  • d)
    A and D
Correct answer is option 'A'. Can you explain this answer?
Verified Answer
Aminoacyl tRNA synthetase face two important challenges, i. they must ...
Concept:
  • Aminoacyl-tRNA synthetases (ARSs) are universal enzymes that catalyze the attachment of amino acids to the 3′ ends of their cognate tRNAs.
  • The resulting amino-acylated tRNAs are escorted to the ribosome where they enter protein synthesis.
  • By specifically matching amino acids to defined anticodon sequences in tRNAs, ARSs are essential to the physical interpretation of the genetic code.
  • In addition to their canonical role in protein synthesis, ARSs are also involved in RNA splicing, transcriptional regulation, translation, and other aspects of cellular homeostasis.
Explanation:
Fig 1: Characteristics of Aminoacyl-tRNA synthetases
 
  • ARSs possess the ability to finely discriminate among different chemically similar amino acid substrates, employing both passive binding and active editing strategies.
  • For those ARSs that aminoacylate hydrophobic amino acids (e.g. IleRS, ValRS, LeuRS, ThrRS, and AlaRS), the amino acid pocket alone provides insufficient discrimination to prevent misacylation of near-cognate amino acids.
  • Thus, amino acid groupings consisting of Ile/Val, Leu/Ile/Met/Val, Val/Thr, Thr/Ser, and Ala/Gly/Ser have imposed selection for editing function in the ARSs associated with the first amino acid in the grouping.
  • In the original “double sieve” model proposed to account for ARS discrimination, an initial “coarse” sieve prevents the binding and activation of larger and chemically dissimilar amino acids, whereas a second “finer” sieve allows amino acids smaller than the cognate to pass through to a second active site.
  • These misacylated substrates undergo hydrolysis by a specific deacylation activity in the editing site.
  • As predicted by this model, ARSs with well-defined editing properties possess separate protein domains dedicated to this editing function.
  • This deacylation mechanism has been referred to as “post-transfer editing”.
  • Alternatively, the misactivated amino acid can be eliminated by hydrolytic decomposition of the adenylate prior to transfer of the amino acid to the tRNA, referred to as “pre-transfer editing”.
  • The relative contribution of these two mechanisms depends on the relative rates of aminoacyl transfer and deacylation.
  • Evidence from both prokaryotic and eukaryotic systems indicates there is a fitness cost for the absence of editing functions.
  • For example, an inbred mouse strain containing an editing-deficient AlaRS allele (the sticky (Sti) allele) exhibits Purkinje cell degeneration and associated deficits in cerebellar function.
​From the above explanation, we can say that statements A and B are correct.
Hence the correct answer is option 1.
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Most Upvoted Answer
Aminoacyl tRNA synthetase face two important challenges, i. they must ...
Understanding Aminoacyl tRNA Synthetase Specificity
Aminoacyl tRNA synthetases play a crucial role in protein synthesis by ensuring that the correct amino acids are attached to their corresponding tRNAs. This process is highly specific and involves various mechanisms to maintain fidelity.
Challenges Faced by Aminoacyl tRNA Synthetases
- Recognition of tRNA: The enzyme must accurately distinguish between different tRNAs that may accept the same amino acid.
- Charging Iso-accepting tRNAs: It must ensure that all iso-acceptors are charged with the correct amino acid.
Mechanisms for High Fidelity
The correct answer is option 'A', which states that:
- Discrimination at the Acceptor Stem:
- The primary site for tRNA recognition and specificity lies in the acceptor stem of the tRNA. This region contains specific nucleotides that are critical for the binding and recognition by aminoacyl tRNA synthetases.
- The structure and sequence of the acceptor stem allow synthetases to distinguish between tRNAs that may appear similar.
Other Options Explained
- Anticodon Loop (Option B):
- While the anticodon loop is vital for mRNA recognition during translation, it plays a lesser role in the initial charging process by aminoacyl tRNA synthetases.
- N-terminus of Aminoacyl Synthetase (Option C):
- Although the N-terminus contributes to overall specificity, it is not the primary site for tRNA recognition.
- Variable Loop of tRNA (Option D):
- The variable loop can provide additional information but is not the main determinant for specificity.
Conclusion
In summary, the high fidelity of aminoacyl tRNA synthetases primarily stems from their ability to discriminate based on the acceptor stem of tRNAs, which is why option 'A' is the correct choice.
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Aminoacyl tRNA synthetase face two important challenges, i. they must recognize the correct set of tRNA for a particular amino acid ii. they must charge all these iso-accepting tRNAs with the correct amino acid, Both these processes are carried out with high fidelity by the possible Mechanism: A. The discrimination ability resides predominantly at the acceptor stem of tRNAs B. The specificity is contributed by anticodon loop in tRNA C. The specificity is embedded in the aminoacyl synthetase at the "N" terminus D. The specificity caused by the variable loop of tRNA Which of the following combinations is correct?a)A and Bb)B and Cc)A and Cd)A and DCorrect answer is option 'A'. Can you explain this answer?
Question Description
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