Signal Sequences Were First Discovered in Proteins Imported into the Rough ER
Signal sequences (and the signal sequence strategy of protein sorting) were first discovered in the early 1970s in secreted proteins that are translocated across the ER membrane as a first step toward their eventual discharge from the cell. In the key experiment, the mRNA encoding a secreted protein was translated by ribosomes in vitro. When microsomes were omitted from this cell-free system, the protein synthesized was slightly larger than the normal secreted protein, the extra length being the N-terminal leader peptide. In the presence of microsomes derived from the rough ER, however, a protein of the correct size was produced. These results were explained by the signal hypothesis, which postulated that the leader serves as an ER signal sequence that directs the secreted protein to the ER membrane and is then cleaved off by a signal peptidase in the ER membrane before the polypeptide chain has been completed (Figure 12-40).
Signal Sequences Were First Discovered in Proteins Imported into the Rough ERSignal sequences (and the signal sequence strategy of protein sorting) were first discovered in the early 1970s in secreted proteins that are translocated across the ER membrane as a first step toward their eventual discharge from the cell. In the key experiment, the mRNA encoding a secreted protein was translated by ribosomes in vitro. When microsomes were omitted from this cell-free system, the protein synthesized was slightly larger than the normal secreted protein, the extra length being the N-terminal leader peptide. In the presence of microsomes derived from the rough ER, however, a protein of the correct size was produced. These results were explained by the signal hypothesis, which postulated that the leader serves as an ER signal sequence that directs the secreted protein to the ER membrane and is then cleaved off by a signal peptidase in the ER membrane before the polypeptide chain has been completed (Figure 12-40).
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