Co-translational targeting and translocation of proteins to the endoplasmic reticulum

Co-translational protein targeting to the endoplasmic reticulum (ER), represents an evolutionary-conserved mechanism to target proteins into the secretory pathway. In this targeting pathway proteins possessing signal sequences are recognised at the ribosome by the signal recognition particle while they are still undergoing synthesis. This triggers their delivery to the ER protein translocation channel, where they are directly translocated into the ER. Here we review the current understanding of this translocation pathway and how molecular details obtained in the related bacterial system have provided insight into the mechanism of targeting and translocation. This article is part of a Special Issue entitled: Functional and structural diversity of endoplasmic reticulum.

► SRP is able to detect signal sequences as they emerge from the ribosome.
► SRP retards translation to create a time window for ER targeting.
► SRP receptor transfers the ribosome nascent chain complex from SRP to the translocon.
► The Sec61 channel conveys the nascent chain from the ribosome directly into the ER lumen.
► Sec61 can also insert membrane proteins into the lipid bilayer.