Thursday, October 21, 2010

the initiation of protein synthesis in eukaryotes

Schematic diagram of initiation of protein synthesis

Note that the process is in principle very similar to prokaryotic initiation.  Major differences from prokaryotic initiation are associated with the m7G cap of the mRNA and its interaction with the cap-binding protein (CBPI) and eIF4F (CBPII) instead of Shine-Dalgarno sequence-mediated alignment to properly position the first AUG codon in the P site of the ribosome and the absence of initiator tRNA-fMet.

Summary

  • Polypeptide synthesis proceeds sequentially from N terminus to C terminus
  • Ribosomes read mRNA only in the 5'->3' direction, never in the 3'->5' direction
  • Active translation typically occurs on polyribosomes
  • Chain elongation links the growing polypeptide to incoming aminoacyl-tRNA
  • Three steps are involved in the synthesis of one polypeptide chain of N residues:
      1.  INITIATION (1 x)
      2.  ELONGATION (N-1 x)
      3.  TERMINATION (1 x)
  • Initiation in prokaryotes requires:
      1.  One empty 70S ribosome
      2.  Three initiation factors:  IF1, IF2, IF3
      3.  mRNA with Shine-Dalgarno sequence and START codon (AUG)
      4.  Initiator fMet-tRNAfMet
      5.  One high-energy phosphate bond from GTP
  • Initiation in eukaryotes is similar, but more complicated (no Shine-Dalgarno, no fMet, 10+ eIFs, etc)

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