Chapter 30: Protein Synthesis

Significant attention is given to the fidelity of protein synthesis, maintained by aminoacyl-tRNA synthetases which activate amino acids via adenylation and utilize proofreading editing sites to ensure correct pairing, such as distinguishing between threonine and serine. The concept of the genetic code is expanded through the wobble hypothesis, explaining how steric freedom in the third codon position allows non-standard base pairing like inosine-uracil interactions. The text provides a step-by-step breakdown of bacterial protein synthesis, starting with initiation where the 16S rRNA binds the Shine-Dalgarno sequence to position the AUG start codon for N-formylmethionine (fMet). It describes the elongation cycle involving the delivery of aminoacyl-tRNAs by Elongation Factor Tu (EF-Tu), the catalytic formation of peptide bonds by the 23S rRNA ribozyme within the peptidyl transferase center, and the translocation of mRNA driven by Elongation Factor G (EF-G) and GTP hydrolysis. The narrative contrasts this with eukaryotic translation, highlighting the larger 80S ribosome, the role of the 5' cap and poly(A) tail in mRNA circularization, and the scanning mechanism used to locate the initiator methionine. Furthermore, the chapter explores the mechanisms of translation inhibitors, detailing how antibiotics like streptomycin, puromycin, and chloramphenicol target bacterial ribosomes, while toxins such as diphtheria and ricin disrupt eukaryotic elongation factors and rRNA. The summary concludes with an explanation of the secretory pathway, describing how signal sequences and the Signal Recognition Particle (SRP) target ribosomes to the endoplasmic reticulum (ER) translocon for the synthesis of membrane and secretory proteins.