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Exploring the Genetic Code for Protein Synthesis Mechanisms

Dive into the intricate processes of genetic code utilization, suppressor mutations, ribosome influence, and translation accuracy in protein synthesis.

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Exploring the Genetic Code for Protein Synthesis Mechanisms

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  1. Peter John M.Phil, PhDAtta-ur-Rahman School of Applied Biosciences (ASAB)National University of Sciences & Technology (NUST)

  2. Using The Genetic Code

  3. Using the Genetic Code-1 • Wobble Base paring • Structure of tRNA • Codon Anticodon Pairing • Modified Bases

  4. Using the Genetic Code-2 • tRNA Charging • Aminoacyle synthetases • Structure, function of synthetases • Proof Reading Mechanism

  5. Using the Genetic Code-3 • Suppressor tRNAs • Mechanism of Suppression • Frame Shifting • Programmed Frame Shifting

  6. Suppressor mutation • A suppressor is a second mutation that restores a function lost by the primary mutation. • A suppressor mutation that occurs within the same gene is called an "intragenic suppressor", and a suppressor mutation that occurs in a different gene is called an "intergenic suppressor"

  7. Suppressor mutation • A mutation that overcome the affect of other mutation is called “suppressor” • Suppressor tRNA restore the function of mutant protein, it may be non-sense/missense • In wild type cell mutation is recognized by release factor which terminate protein synthesis. • If different AA is inserted than the original one then active protein is alerted

  8. Suppressor tRNAs • A suppressor tRNA typically has a mutation in the anticodon that changes the codons to which it responds. • When the new anticodon corresponds to a termination codon, an amino acid is inserted and the polypeptide chain is extended beyond the termination codon. • This results in nonsense suppression at a site of nonsense mutation or in read through at a natural termination codon.

  9. Stop Codon Suppressor • Amber Suppressor (UGA) • Ochre Suppressor (UAA, UAG)

  10. Suppressor Compete With Wild Type • Non Sense suppressor tRNA compete with release factor that recognize stop codon • A missense suppressor tRNA compete with tRNA that respond properly to its new codon • The effectiveness of a suppressor depends upon its affinity & its concentration in the cell

  11. Suppressor Compete With Wild Type • Non sense suppressor may also suppress stop codon causing read through & elongation of protein, which can be deleterious • Amber suppressor (UAG) are active (10-50%) depending upon the environment • Ochre suppressor (UAA, UAG) below 10% • UAG is misread by Trp-tRNA (1-3%)

  12. Suppressor tRNA • Suppressor tRNA have 2 consequence • (i) It recognize new codon • (ii) some time prevent tRNA to respond

  13. Mechanism of suppression

  14. Ribosome Influence Translation Accuracy • Two stages when error can occur in protein synthesis • (i) Charging a tRNA with correct AA • (ii) Codon/anti codon binding • Ribosome & tRNA also influence protein binding Codon & anticodon

  15. Ribosome Influence Translation Accuracy • Two model that ribosome discriminate b/w correct & incorrect tRNA • Direct recognition model: in proper/normal binding conformational change occur in aminoacyle tRNA, which ribosome can recognize • Kinetic Proof Reading Model: An incorrect aminoacyle tRNA can pas through some stages before its degradation

  16. Ribosome Influence Translation Accuracy

  17. change in codon meaning • Suppression involve recognition of a codon by mutant tRNA that usually respond to different codon • Re definition of the meaning of a codon occurs when an aminoacyle tRNA is modified. • The reading frame can be changed by framshifting or bypassing, both of which depending upon the properties of the mRNA.

  18. Frame shifting • Frame shifting occur in 2 ways • (i) some mutant tRNA recognize 4 bp codon instead of 3 bp • (ii) slippery seq allow tRNA to move base up/down mRNA in the A site

  19. Frame shifting

  20. Programmed Frame shifting • Some times frame shifting is important for the expression of certain genes, this is called programmed frame shifting • Delay in ribosome can also cause frame shifting

  21. By Passing • By Pass can occur due to • (i) Ribosomal delay • (ii) Starvation in Amino Acid • ribosome miss one stop codon & termination occur at other, when identical (or synonymous) codons at either end of the sequence that is skipped. • They are sometimes referred to as the "take-off" and "landing" sites.

  22. By Passing

  23. Thanks

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