ABSTRACT

T he transport o f proteins across biological membranes is a process fundamental to intracellular protein trafficking and organelle biogenesis. Entry into the eukaryotic secretory pathway is initiated by the translocation ofproteins across the membrane o f the endoplasmic reticulum (ER). This occurs at the translocon, a specialised proteinaceous structure embedded in the membrane o f the ER . The translocon mediates the transport o f soluble proteins from the cytosol to the ER lu­ men and also the transfer o f transmembrane domains o f membrane proteins into the lipid bilayer o f the E R membrane. Extensive modifications to protein structure also occur in the E R and after their biogenesis is complete, proteins are trafficked to their final subcellular destination or secreted from the cell. W hilst it has become clear that the protein conducting pore o f the translocon is formed by the Sec61 complex, the precise nature o f the functional translocon has yet to be ascertained. A com­ bination o f genetic, cell biology and biochemical studies in yeast has led not only to the identification o f the components o f the Sec61 complex, but also a number o f additional components required for E R protein translocation. The roles o f these components and in particular those that associate with the Sec61 complex to form the larger S E C complexes will be the focus o f this chapter.