Signalpeptide

Signal peptides are short amino-terminal extensions that direct newly synthesized proteins to the secretory pathway. Most are 15 to 30 amino acids in length and are typically cleaved from the mature protein after targeting. They direct proteins to the endoplasmic reticulum in eukaryotes and to the Sec pathway in bacteria, enabling secretion or insertion into membranes of the secretory system. A canonical signal peptide comprises three regions: a positively charged n-region, a hydrophobic h-region, and a polar c-region containing a cleavage site for signal peptidase. Many belong to an AxA motif that is recognized by the signal peptidase.

Mechanism and fate: During translation, the signal recognition particle binds the signal peptide as it emerges from the ribosome, pausing translation and guiding the ribosome–nascent chain to a receptor on the endoplasmic reticulum membrane. The polypeptide is then translocated through or embedded in the Sec61 translocon. If destined for secretion, the protein enters the ER lumen and proceeds through the secretory pathway; the signal peptide is typically removed by signal peptidase. In some cases the signal sequence also serves as a membrane anchor and is not cleaved, producing a type I membrane protein or a tail-anchored protein.

Variations and scope: While the classic signal peptide directs proteins toward the secretory pathway, other targeting signals exist for different organelles and contexts, such as lipoprotein signals in bacteria and distinct presequences for mitochondria and chloroplasts. These elements share the general role of guiding polypeptides to their proper cellular location.