Signal Peptides

Signal peptides are peptide moieties containing approximately 13–36 amino acid residues that are present in the N-terminus of membrane-bound proteins and secreted proteins. Signal peptides are hydrophobic peptides that are recognized by signal recognition particle (SRP) as the protein emerges through the ribosome exit side. The complex between signal peptide and SRP induces translational elongation arrest in the endoplasmic reticulum (ER) and then binds to the SRP receptor (SR) which is associated with translocon. Thus, the nascent polypeptide extrudes into the ER lumen through the association with SR and translocon. Upon passage through the ER, the signal peptide is cleaved by signal peptidases. Signal peptidases are highly sequence-specific enzymes and efficiently remove the signal peptides that are complementary to the protein sequence. Signal peptide sequences are designed for the efficient secretion of many proteins including RTPs expressed in many different host cells. If the signal peptides are not complementary to the sequence of the protein, the signal peptidase may not cleave the signal peptides completely. The uncleaved signal peptides might present potential safety risks including immunogenicity.