10.5:
Termination of Translation
Once an mRNA is translated, the ribosome needs to dissociate from the RNA and release the newly made polypeptide chain.
Translation is terminated when a stop codon, UAA, UAG, or UGA, is encountered. There are no complementary tRNAs that correspond to stop codons.
Instead, when a stop codon is positioned on the A site of the ribosome, it is recognized by proteins called release factors, RF1 or RF2.
This binding forces the enzyme peptidyl transferase in the ribosome to catalyze the addition of a water molecule instead of an amino acid to the peptidyl-tRNA.
As a result, the P-site amino acid detaches from its tRNA, releasing the newly made polypeptide into the cytoplasm.
Next, a third release factor, RF3, bound to GDP joins the ribosome.
On the ribosome, RF3 replaces GDP with GTP. This exchange brings about a conformational change in RF3, which triggers the dissociation of RF1 and RF2 from the ribosome.
Then, RF3 catalyzes GTP hydrolysis, which allows the ribosomal subunits to dissociate from each other and from the mRNA.
The disassembled ribosomal subunits bound to an initiator tRNA, can now join a new mRNA for another round of translation.
10.5:
Termination of Translation
The large ribosomal subunit has several important structures essential to translation. These include the peptidyl transferase center (PTC) – which is the site where the peptide bond is formed – and a large, internal, water-filled tube through which the nascent polypeptide moves. This latter structure is called the Peptide Exit Tunnel, and it begins at the PTC and spans the body of the large ribosomal subunit. During translation, as the nascent polypeptide chain is synthesized, it passes through the peptide exit tunnel. It then emerges out in the solvent side, where the peptide chain is subsequently folded into a protein.
This tunnel formed by the 23S ribosomal RNA creates a large hydrophilic surface, containing tiny hydrophobic patches. The dimensions of the tunnel (approximately 10 nm × 1.5 nm) can accommodate growing, unstructured polypeptide chains, as well as solvent molecules. The interior of the peptide exit tunnel is not complementary to any peptide. Hence, the polypeptide chain does not “stick” to the walls and can easily slide through. Once it reaches a location in the exit tunnel where there is sufficient space, the nascent peptide chain starts to fold and may successfully form some α-helical regions. However, the majority of protein folding occurs once the polypeptide exits the ribosome.
Suggested Reading
- Alberts, Bruce. "Molecular Biology of the Cell." (2016), Pgs 348-349.
- Voss, N. R., M. Gerstein, T. A. Steitz, and P. B. Moore. "The geometry of the ribosomal polypeptide exit tunnel." Journal of molecular biology 360, no. 4 (2006): 893-906.
- Kudva, Renuka, Pengfei Tian, Fátima Pardo-Avila, Marta Carroni, Robert B. Best, Harris D. Bernstein, and Gunnar Von Heijne. "The shape of the bacterial ribosome exit tunnel affects cotranslational protein folding." Elife 7 (2018): e36326.