Fundamentals of Molecular Biology. Part 2: Molecular Genetic Mechanisms - A. N. Ogurtsov 2011

Protein synthesis on ribosomes
Translation termination

The final stage of Translation, much like initiation and elongation, requires specific molecular signals that translate the stop signal of a stop codon into the dissociation of the mRNA—ribosome—tRNA—polypeptide complex (Figure 46).

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Figure 46 - Translation termination in eukaryotes

Two distinct protein termination factors have been identified, known as polypeptide release factors (RF). Eukaryotic eRF1, which mimics the shape of a tRNA molecule, appears to function by binding directly to the A-site and directly recognizing the stop codon.

Similar to certain initiation and elongation factors, the eRF3 release factor is associated with GTP. The binding of the (eRF3-GTP) complex to eRF1, coupled with ATP Hydrolysis, drives the release of the polypeptide from the tRNA and completes Protein Synthesis (Figure 46).

Unlike eukaryotes, Bacteria possess two release factors, RF1 and RF2 (which are functionally analogous to the eukaryotic eRF1), as well as a GTP-binding factor RF3, which corresponds to eRF3.

Upon release from the ribosome, the newly synthesized protein is folded into its native three-dimensional conformation with the assistance of specialized chaperone Proteins.

The eRF3 protein termination factors facilitate

1) ribosome dissociation,

2) the Separation of the ribosomal subunits, mRNA, and the final tRNA, which are now primed to participate in a new round of protein synthesis.

Every stage of translation proceeds with the involvement of GTP-binding proteins. These proteins belong to the GTPase superfamily—molecular switches that cycle between an active GTP-bound state and an inactive GDP-bound state (Figure 47).

The hydrolysis of GTP bound to the GTPase induces a conformational change in either the GTPase itself or its interacting proteins, triggering the switch mechanism in numerous molecular processes.

For instance, during Translation initiation, the hydrolysis of (eIF2-GTP) to (eIF2-GDP) upon reaching the start codon halts mRNA scanning and permits the joining of the large and small ribosomal subunits (Figure 42, step 3).

Similarly, the hydrolysis of (EF2-GTP) to (EF2-GDP) during elongation drives the translocation of the ribosome along the mRNA (Figure 43, step 4).

Figure 47 - Cycling between the active and inactive states of GTPase molecular switches. GTPase activation is accelerated by GAPs (GTPase-activating proteins) and RGSs (regulators of G-protein signaling) and inhibited by GDIs (guanine nucleotide dissociation inhibitors). GTPase reactivation is mediated by GEFs (guanine nucleotide-exchange factors)