Cotranslational Membrane Protein Biogenesis at the Endoplasmic Reticulum

In eukaryotic cells, most polypeptides destined to become membrane proteins are initially integrated into the membrane of the endoplasmic reticulum (ER)1 before being sorted to the location at which they function. Integration occurs at sites in the ER membrane termed translocons that are comprised of a specific set of membrane proteins (1, 2). In most cases, proteins are integrated into the bilayer cotranslationally, i.e. at the same time that they are being synthesized by ribosomes. During this process, the biosynthetic machinery mediates the integration of transmembrane sequences (TMSs) into the nonpolar core of the bilayer and delivers aqueous cytoplasmic and luminal domains to the appropriate compartments.