Protein insertion into the membrane of the endoplasmic reticulum: The architecture of the translocation site

In mammalian cells, most membrane proteins are inserted cotranslationally into the membrane of the endoplasmic reticulum (ER), and secretory proteins are translocated across this membrane (for review, see Rapoport 1992). These processes are initiated in the cytoplasm by binding of the signal sequence of the na-scent polypeptide chain to the signal recognition parti-cle (SRP) (Walter and Blobel 1981). The resulting ribosome nascent chain SRP complex is then targeted to the ER membrane by an interaction with the mem-brane-bound SRP receptor (docking protein) (Gilmore et al. 1982; Meyer et al. 1982). At the membrane, the signal sequence is released from SRP in a GTP-requiring step, and the nascent polypeptide is trans-ferred into the ER translocation site (Connolly an