A simplified view of protein translocation across the ER membrane, as originally proposed. When the ER signal sequence emerges from the ribosome, it directs the ribosome to a translocator on the ER membrane that forms a pore in the membrane through which the polypeptide is translocated. The signal sequence is clipped off during translation by a signal peptidase, and the mature protein is released into the lumen of the ER immediately after being synthesized. We now know that the hypothesis is correct in outline but that additional components besides those shown in this figure are required.