Three epochs of nascent protein translocation through the ribosome exit tunnel

published 2024-04-20

Proteins and peptides are fundamental to life. In all organisms, these molecules are synthesized by the ribosome — a large ribonucleoprotein complex — in a process known as translation. During this process, the nascent protein remains tethered to the ribosome for a significant duration. In our new study, we conceptualize this phase of the protein's life by dividing it into three distinct epochs. These epochs are characterized based on the position of the nascent polypeptide's N-terminus within the ribosome exit tunnel and its relationship to the catalytic center.

A preprint is now available an arXiv.

During Epoch I, the N-terminus of the nascent protein travels from the catalytic center of the ribosome through the tunnel, presumably in the extended conformation. It passes through a constriction of the tunnel and enters a vestibule of the outer part of the tunnel. After the N-terminal residue is cleaved off from the nascent protein by ribosome biogenesis factors, Epoch II begins. It covers the time required to synthesize the remaining portion of the nascent protein. Translocation through the tunnel during Epoch II is mainly driven by folding of the nascent protein in the native tertiary structure outside the ribosome. Finally, Epoch III represents the escape of the released C-terminus from the PTC to the surface of the ribosome.