Membrane protein targeting is a fundamental problem in cell biology. Pioneering work by George Palade in the 1960s established that the endoplasmic reticulum (ER) is the entry point for most proteins along the secretory/endocytic pathway. ER protein targeting information was later shown by Gunter Blobel and colleagues to reside in N-terminal signal sequences and start-transfer signals. Much research since then has revealed that the signal recognition particle (SRP) binds to these hydrophobic sequences upon their emergence from the ribosome and escorts them to the SRP receptor in the ER membrane for co-translational protein translocation by the Sec61 translocon.
