peptidyl transferase and translocation

Two distinct things have to happen in every round of elongation, and it helps to keep them straight. First a new amino acid must be chemically welded onto the growing chain. Then the whole ribosome must shuffle forward to line up the next codon. The first is done by an activity called peptidyl transferase; the second is translocation. Together they are the chemistry and the choreography of building a protein.

Peptidyl transferase is the reaction that forms the peptide bond. Sitting in the large subunit, it takes the entire chain held on the P-site tRNA and joins it to the amino acid waiting on the A-site tRNA, leaving the lengthened chain now hanging on the A-site tRNA. The astonishing part is what does this: not a protein enzyme, but the ribosomal RNA itself. The catalytic centre is built from RNA, making the ribosome a ribozyme — strong evidence that RNA-based catalysis is ancient. Translocation is the movement that follows: the ribosome ratchets along the mRNA by exactly one codon, sliding the spent tRNA into the E site, the chain-bearing tRNA into the P site, and exposing a fresh codon in the now-empty A site. This step is driven by an elongation factor spending GTP, and it is what keeps the reading frame from slipping.

Splitting these two events explains why the protein chain grows the way it does and why translation stays in frame. Peptidyl transferase explains why the chain is always handed forward onto the newest amino acid (the chain moves to the A site, not the other way), and why the freshly made bond is a peptide bond identical to the ones in every protein. Translocation explains the directional, exactly-three-bases-at-a-time march. Several antibiotics target precisely one of these two acts — chloramphenicol blocks the peptidyl transferase reaction, while others freeze translocation — which is why understanding the split is more than bookkeeping.