anticodon
Summary
The anticodon is a 3-nucleotide sequence on the anticodon loop of tRNA that base-pairs (antiparallel) with the complementary mRNA codon during translation at the ribosome. It ensures the correct amino acid is added to the growing polypeptide chain. Wobble at the 3' position of the codon (5' position of the anticodon) allows one tRNA to recognize multiple codons.
Detail
STRUCTURE/LOCATION: The anticodon lies in the anticodon loop (one of the tRNA's stem-loops) of the cloverleaf-shaped tRNA. The amino acid is attached at the 3' CCA end (acceptor stem) via an ester bond. The T-psi-C arm binds the ribosome, and the D arm is the site recognized by aminoacyl-tRNA synthetase.
BASE PAIRING: The anticodon pairs with the mRNA codon in an antiparallel fashion. Example: mRNA codon 5'-AUG-3' pairs with the anticodon 5'-CAU-3' (tRNA-Met). Anticodons are conventionally written 5'→3'. Codon position 1 pairs with anticodon position 3, and codon position 3 pairs with anticodon position 1.
WOBBLE HYPOTHESIS: Codon position 3 (the 3' base of the codon) pairs less strictly with anticodon position 1 (the 5' base of the anticodon). This explains why ~31 tRNAs can decode 61 sense codons, and why the genetic code is degenerate/redundant (often the third base is the "wobble" base). Inosine (from deamination of adenosine in the anticodon) can pair with U, C, or A. G can pair with U or C.
FIDELITY STEPS: Accuracy depends on two steps. (1) Aminoacyl-tRNA synthetase charges the correct amino acid onto the matching tRNA (uses 2 high-energy phosphate bonds from ATP, has proofreading activity, and is the real "second genetic code"). The ribosome does not check the amino acid, so a mischarged tRNA delivers the wrong amino acid. (2) Codon-anticodon matching in the ribosomal A site (with proofreading by the ribosome and EF-Tu/EF-1 GTP hydrolysis).
TRANSLATION CONTEXT: Charged tRNA enters the A site (EF-Tu in prokaryotes; eEF-1α in eukaryotes), peptidyl transferase forms the peptide bond (23S rRNA in prokaryotes / 28S rRNA in eukaryotes, a ribozyme), then translocation (EF-G / eEF-2) moves the tRNA to the P site, then the E site. Stop codons (UAA, UAG, UGA) have NO corresponding tRNA anticodon and are recognized by release factors.
CLINICAL CORRELATIONS: - Point mutations: A mutation in the mRNA codon changes which anticodon pairs (missense, nonsense, silent mutations). Silent mutations are often at the wobble position. - Antibiotics affecting tRNA binding: Tetracyclines block aminoacyl-tRNA binding to the A site (30S subunit). Aminoglycosides (30S) cause misreading of the codon and interfere with initiation. Macrolides/clindamycin block translocation (50S). Chloramphenicol inhibits peptidyl transferase (50S). Linezolid blocks initiation complex formation (50S). - Mitochondrial tRNA mutations cause diseases such as MELAS (mtDNA tRNA-Leu mutation) and MERRF (tRNA-Lys mutation); both show maternal inheritance and heteroplasmy, with ragged red fibers on muscle biopsy. - Suppressor tRNAs: Mutated anticodons that read through premature stop codons (an experimental therapeutic strategy). - Selenocysteine (the 21st amino acid) is decoded by a tRNA with an anticodon that reads UGA under special conditions (SECIS element).
HIGH-YIELD PEARLS: tRNA is the most abundant post-transcriptionally modified RNA (modified bases include pseudouridine, dihydrouridine, inosine). tRNA is transcribed by RNA polymerase III. Initiator tRNA is Met (eukaryotes, AUG) or fMet (prokaryotes, N-formylmethionine). The 3' CCA is added post-transcriptionally. "Charged" tRNA = tRNA with its amino acid attached.
Sources
- First Aid for the USMLE Step 1 (Biochemistry: Genetics - tRNA, Protein synthesis)
- Lippincott Illustrated Reviews: Biochemistry (Ch. 31 Protein Synthesis)
- Pathoma / Sketchy Biochemistry (Translation and tRNA)
- Lehninger Principles of Biochemistry (Protein Metabolism)
- Harper's Illustrated Biochemistry (Protein Synthesis and the Genetic Code)
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