Membrane translocation at the ER: with a little help from my friends.

The Sec61 complex is the proteinaceous pore through which one-third of mammalian polypeptides access the lumen of the endoplasmic reticulum (ER) during their translocation across, or insertion into, the ER membrane. N-terminal ER signal peptides mediate polypeptide targeting to, and opening of, the Sec61 channel in a substrate-specific manner. Here, we discuss the recently defined features of ER signal peptides which necessitate the use of the accessory components Sec62 and Sec63 during the Sec61-mediated cotranslational translocation of newly synthesized secretory proteins.