Origins and evolution of cotranslational transport to the ER

Abstract

All living organisms possess the ability to translocate proteins across biological membranes. This is a fundamental necessity since proteins function in different locations yet are synthesized in one compartment only, the cytosol. Even though different transport systems exist, the pathway that is dominantly used to translocate secretory and membrane proteins is known as the cotranslational transport pathway. It evolved only once and is in its core conserved throughout all kingdoms of life. The process is characterized by a well understood sequence of events: first, an N-terminal signal sequence of a nascent polypeptide is recognized on the ribosome by the signal recognition particle (SRP), then the SRP-ribosome complex is targeted to the membrane via the SRP receptor. Next, the nascent chain is transferred from SRP to the protein conducting channel, through which it is cotranslationally threaded. All the essential components of the system have been identified. Recent structural and biochemical studies have unveiled some of the intricate regulatory circuitry of the process. These studies also shed light on the accessory components unique to eukaryotes, pointing to early events in eukaryotic evolution.