Translation elongation and termination

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  • Translation elongation and termination
    • ribosome processes along the mRNA, adding AAs to the nascent polypeptide chain
      • arrival of next AA in the sequence and its addition through formation of polypeptide bond causes ribosome to move along to the next codon
        • called TRANSLOCATION
          • aided by elongation factors (EFs)
    • 3 important sites
      • A site
        • acceptor site - where the aminoacyl tRNA lands charged with the next AA to be added
      • P site
        • peptidyl-tRNA site, occupied by the most recent aminoacyl tRNA
      • E site
        • exit site - where the tRNA due to leave the ribosome following delivery of its associated AA is temporarily located
      • located primarily in the large subunit
        • but A P E sites can only form when 2 subunits are associated
    • translation initiation
      • initial tRNA carrying methionine AA is located to P site
        • next tRNA joins, entering the A site
          • aided by elongation factor EF1a bound to a molecule of GTP
          • after GTP hydrolysis, a peptide bond is formed between the AAs
            • reaction catalysed by the ribozyme activity of the rRNA itself
            • translocation occurs
              • aided by EF2 and hydrolysis of the GTP molecule it carries
              • initiator tRNAiMet has now lost its methionine and is moved to the E site, the 2nd tRNA shifts to the P site, allowing a new incoming charged tRNA to enter the A site
                • polypeptide synthesis ends with translation termination
                  • release factors recognise stop codons
                    • help to release the nascent polypeptide from the mRNA
                  • when ribosome reaches a stop codon, eRF1 docks near the A site in association with eRF3
                    • GTP hydrolysis promotes cleavage of the complete polypeptide from the last tRNA and dissociation from the ribosome
                      • ribosome subunits then free to begin another round of translation
        • (methionine is anticodon for AUG)
    • signal recognition particles
      • used for proteins that are destined for secretion from the cell or for insertion into cellular membranes
      • RNA-protein complex which binds to a short signal sequence present at the N-terminus of such proteins and mediates their targeting
        • signal sequence = short order of about 12 hydrophobic AAs
      • binds to signal sequence while the protein is still being translated
        • leads to arrest in translation and targeting of the ribosome-polypeptide-SRP complex to the endoplasmic reticulum
          • SRP interacts with the membrane-bound SRP receptor on the ER membrane and transfers the polypeptide-ribosome complex onto a translocon protein in the ER membrane
            • the translocon serves as a pore, allowing the newly-synthesised protein to be inserted within the membrane
              • the remaining section of translation then takes place through the pore, allowing the protein to either be inserted into the ER membrane
                • this requires a 2nd signal sequence along the polypeptide called a topogenic sequence
                • or into the ER lumen, where it can be modified and sent along the rest of its cellular journey before reaching its target destination


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