64 codons (43): 61 code for amino acids, 3 stop (UAA, UAG, UGA); AUG starts with methionine (fMet in prokaryotes). The code is degenerate but unambiguous and nearly universal.
Wobble at the third codon position explains degeneracy and why silent mutations cluster there.
Ribosomes and the Elongation Cycle
Prokaryotic 70S (30S + 50S) vs. eukaryotic 80S (40S + 60S). The A site accepts charged tRNA, the P site holds the growing peptide, the E site releases spent tRNA.
Initiation: Shine-Dalgarno pairing in prokaryotes; 5' cap scanning to a Kozak-context AUG in eukaryotes. Peptide bonds are formed by peptidyl transferase — an rRNA ribozyme. Translocation needs EF-G (or eukaryotic EF-2, the target of diphtheria toxin). Release factors mimic tRNA at stop codons.
Aminoacyl-tRNA synthetases charge each tRNA with its amino acid using ATP — the "second genetic code," complete with proofreading.
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30S targets: tetracycline (blocks the A site), aminoglycosides (cause misreading). 50S targets: chloramphenicol, macrolides, clindamycin, linezolid. Puromycin mimics tRNA and terminates chains prematurely.
Post-translational control includes glycosylation, phosphorylation, ubiquitination, and zymogen cleavage.
Key Takeaways
Map every step to A, P, and E sites.
The ribosome is a ribozyme — catalysis lives in the rRNA.
Synthetase fidelity, not codon reading alone, guarantees accurate translation.
Sort translation antibiotics by 30S vs. 50S subunit.