Biology

Protein synthesis occurs by initiation, elongation, and termination

KEY TERMS:

The A site of the ribosome is the site that an aminoacyl-tRNA enters to base pair with the codon.
The P site of the ribosome is the site that is occupied by peptidyl-tRNA, the tRNA carrying the nascent polypeptide chain, still paired with the codon to which it bound in the A site.
Peptidyl-tRNA is the tRNA to which the nascent polypeptide chain has been transferred following peptide bond synthesis during protein synthesis.
Deacylated tRNA has no amino acid or polypeptide chain attached because it has completed its role in protein synthesis and is ready to be released from the ribosome.
Translocation is the movement of the ribosome one codon along mRNA after the addition of each amino acid to the polypeptide chain.
Elongation is the stage in a macromolecular synthesis reaction (replication, transcription, or translation) when the nucleotide or polypeptide chain is being extended by the addition of individual subunits.
Termination is a separate reaction that ends a macromolecular synthesis reaction (replication, transcription, or translation), by stopping the addition of subunits, and (typically) causing disassembly of the synthetic apparatus.

KEY CONCEPTS:

The ribosome has 3 tRNA-binding sites.
An aminoacyl-tRNA enters the A site.
Peptidyl-tRNA is bound in the P site.
Deacylated tRNA exits via the E site.
An amino acid is added to the polypeptide chain by transferring the polypeptide from peptidyl-tRNA in the P site to aminoacyl-tRNA in the A site.

An amino acid is brought to the ribosome by an aminoacyl-tRNA. Its addition to the growing protein chain occurs by an interaction with the tRNA that brought the previous amino acid. Each of these tRNA lies in a distinct site on the ribosome. Figure 6.3 shows that the two sites have different features:

An incoming aminoacyl-tRNA binds to the A site. Prior to the entry of aminoacyl-tRNA, the site exposes the codon representing the next amino acid due to be added to the chain.
The codon representing the most recent amino acid to have been added to the nascent polypeptide chain lies in the P site. This site is occupied by peptidyl-tRNA, a tRNA carrying the nascent polypeptide chain.

Figure 6.4 shows that the aminoacyl end of the tRNA is located on the large subunit, while the anticodon at the other end interacts with the mRNA bound by the small subunit. So the P and A sites each extend across both ribosomal subunits.

For a ribosome to synthesize a peptide bond, it must be in the state shown in step 1 in Figure 6.3, when peptidyl-tRNA is in the P site and aminoacyl-tRNA is in the A site. Then peptide bond formation occurs when the polypeptide carried by the peptidyl-tRNA is transferred to the amino acid carried by the aminoacyl-tRNA. This reaction is catalyzed by the large subunit of the ribosome.

Transfer of the polypeptide generates the ribosome shown in step 2, in which the deacylated tRNA, lacking any amino acid, lies in the P site, while a new peptidyl-tRNA has been created in the A site. This peptidyl-tRNA is one amino acid residue longer than the peptidyl-tRNA that had been in the P site in step 1.

Then the ribosome moves one triplet along the messenger. This stage is called translocation. The movement transfers the deacylated tRNA out of the P site, and moves the peptidyl-tRNA into the P site (see step 3). The next codon to be translated now lies in the A site, ready for a new aminoacyl-tRNA to enter, when the cycle will be repeated. Figure 6.5 summarizes the interaction between tRNAs and the ribosome.

The deacylated tRNA leaves the ribosome via another tRNA-binding site, the E site. This site is transiently occupied by the tRNA en route between leaving the P site and being released from the ribosome into the cytosol. So the flow of tRNA is into the A site, through the P site, and out through the E site (see also Figure 6.28). Figure 6.6 compares the movement of tRNA and mRNA, which may be thought of as a sort of ratchet in which the reaction is driven by the codon-anticodon interaction.

Protein synthesis falls into the three stages shown in Figure 6.7:

Initiation involves the reactions that precede formation of the peptide bond between the first two amino acids of the protein. It requires the ribosome to bind to the mRNA, forming an initiation complex that contains the first aminoacyl-tRNA. This is a relatively slow step in protein synthesis, and usually determines the rate at which an mRNA is translated.
Elongation includes all the reactions from synthesis of the first peptide bond to addition of the last amino acid. Amino acids are added to the chain one at a time; the addition of an amino acid is the most rapid step in protein synthesis.
Termination encompasses the steps that are needed to release the completed polypeptide chain; at the same time, the ribosome dissociates from the mRNA.

Different sets of accessory factors assist the ribosome at each stage. Energy is provided at various stages by the hydrolysis of GTP.

During initiation, the small ribosomal subunit binds to mRNA and then is joined by the 50S subunit. During elongation, the mRNA moves through the ribosome and is translated in triplets. (Although we usually talk about the ribosome moving along mRNA, it is more realistic to think in terms of the mRNA being pulled through the ribosome.) At termination, the protein is released, mRNA is released, and the individual ribosomal subunits dissociate in order to be used again.

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Biology