Translation: Protein Synthesis

Translation: Components - The Protein Factory Crew

• Ribosomes: Site of protein synthesis.
  • Prokaryotes: 70S (50S+30S); Eukaryotes: 80S (60S+40S).
  • Sites: A (aminoacyl), P (peptidyl), E (exit).
• mRNA: Carries genetic code as codons (AUG start; UAA, UAG, UGA stop).
• tRNA: Anticodon pairs with mRNA codon; 3'-CCA attaches specific amino acid.
• Aminoacyl-tRNA Synthetases: "Charge" tRNAs; crucial proofreading.

⭐ Ribosomal RNA (rRNA) in the large subunit (e.g., 23S in prokaryotes, 28S in eukaryotes) possesses peptidyl transferase activity, making it a ribozyme.

Translation: Initiation - Ready, Set, Synthesize!

Prokaryotic Initiation (forms 70S complex):

• mRNA's Shine-Dalgarno sequence (📌 S-D for Small ribosome) aligns with 16S rRNA (30S subunit).
• Initiation Factors: IF1, IF2-GTP (binds fMet-tRNA), IF3.
• Initiator tRNA: fMet-tRNA directly to P-site.

Eukaryotic Initiation (forms 80S complex):

• 40S subunit (with Met-tRNA, eIF2-GTP) binds mRNA's 5' cap, scans to Kozak sequence (📌 Kozak for euKaryotes) around AUG.
• Initiation Factors: Multiple eIFs (e.g., eIF4E binds cap).

⭐ In prokaryotes, the Shine-Dalgarno sequence on mRNA base-pairs with a complementary sequence on the 16S rRNA of the 30S ribosomal subunit to position it correctly for initiation.

Translation: Elongation - Building the Chain

• Polypeptide chain grows via a cycle. 📌 APE sites: Aminoacyl, Peptidyl, Exit.
• Elongation Cycle (GTP-powered):
  • 1. Codon Recognition: aa-tRNA + EF-Tu/eEF1A enters A-site.
  • 2. Peptide Bond Formation: Peptidyl transferase (rRNA) forms peptide bond; chain moves to A-site tRNA.
  • 3. Translocation: EF-G/eEF2 moves ribosome; tRNAs shift (A→P, P→E & exit).

⭐ EF-Tu (prokaryotes) or eEF1A (eukaryotes) is responsible for bringing the charged aminoacyl-tRNA to the A site of the ribosome, a step requiring GTP hydrolysis.

Translation: Termination - It's a Wrap!

• Stop Codons: UAA, UAG, UGA. 📌 (U Are Away, U Go Away, U Are Gone).
• Release Factors (RFs):
  • Prokaryotes: RF1, RF2, RF3.
  • Eukaryotes: eRF1, eRF3.
• Mechanism:
  • RFs bind stop codon at A-site.
  • Polypeptide hydrolysis from tRNA.
  • Ribosomal subunits, mRNA, tRNA dissociate.

⭐ Stop codons are recognized by protein Release Factors (RFs), not by tRNAs, leading to the termination of translation.

Post-Translational Mods - Protein's Extreme Makeover

• Protein Folding: Chaperones (e.g., Hsp70) ensure correct 3D structure.
• Covalent Modifications:
  • Phosphorylation, glycosylation, ubiquitination.
  • Acetylation, methylation, proteolytic cleavage.
  • Disulfide bond formation.
• Significance: Critical for protein function, stability, and diversity.

⭐ Glycosylation, the addition of sugar moieties to proteins, typically begins in the endoplasmic reticulum and continues in the Golgi apparatus, crucial for protein folding, stability, and targeting.

Protein Synthesis Inhibitors - Antibiotic Hit List

📌 Mnemonic: "Buy AT 30, CCELL at 50"

High‑Yield Points - ⚡ Biggest Takeaways

• Translation occurs on ribosomes (70S prokaryotes, 80S eukaryotes), decoding mRNA to protein.
• mRNA codons pair with tRNA anticodons carrying specific amino acids.
• Initiation: AUG start codon (Met); Shine-Dalgarno (prok) / Kozak sequence (euk).
• Elongation: Peptidyl transferase (rRNA ribozyme) forms peptide bonds in A, P, E sites.
• Termination: Stop codons (UAA, UAG, UGA) trigger release of polypeptide.
• Key inhibitors: Many antibiotics (tetracyclines, macrolides) target 70S ribosomes.