Food Chemistry and Fish in Nutrition ( 2+1)

8.3.1.1. Initiation

Initiation of protein synthesis requires that an mRNA molecule be selected for translation by a ribosome. Once the mRNA binds to the ribosome, the latter finds the correct reading frame on the mRNA, and translation begins. This process involves tRNA, rRNA, mRNA, and at least 10 eukaryotic initiation factors (eIFs), some of which have multiple (three to eight) subunits. Also involved are GTP, ATP, and amino acids. Initiation can be divided into four steps;

(1) Dissociation of the ribosome into its 40S and 60S subunits

(2) Binding of a ternary complex consisting of met-tRNA, GTP, and eIF-2 to the 40S ribosome to form a preinitiation complex

(3) Binding of mRNA to the 40S preinitiation complex

(4) Combination of the 40S initiation complex with the 60S ribosomal subunit to form the 80S initiation complex

1) Dissociation of the ribosome

Two initiation factors, eIF-3 and eIF-IA, bind to the 40S subunit. This favors dissociation of the 80S ribosome into its 40S and 60S subunits and prevents ressociation.

2)Formation of the 40S preinitiation complex

Formation of the 40S preinitiation complex involves the binding of GTP by eIF-2. This binary complex then binds to met-tRNA, a tRNA specifically involved in binding to the initiation codon AUG. This ternary complex binds to the 40S ribosomal subunit to form the 40S preinitiation complex, which is stabilized by as sociation with eIF-3 and eLF-1A.

3) Formation of the 40S initiation complex

The 5' terminals of most mRNA molecules in eukaryotic cells are “capped,”. This methyl-guanosyl triphosphate cap facilitates the binding of mRNA to the 40S preinitiation complex. A cap binding protein complex, eIF-4F, binds to the cap through one of its subunits. Then eIF-4F and eIf-4B bind and probably reduce the complex secondary structure of the 5'end of the
mRNA through their respective ATP ase and helicase activities.

4) Formation of the 80S initiation complex

The binding of the 60S ribosomal subunit to the 40S initiation complex involves the hydrolysis of the GTP bound to eIF-2 by eIF-5. This reaction results in the release of the initiation factors bond to the 40S initiation complex. These factors are then recycled and lead to the rapid association of the 40S and 60S subunits to from the 80S ribosome. At this point, the met-tRNA is on the p site of the ribosome, ready for the elongation cycle to commerce.