preproteins

A preprotein is a nascent polypeptide that contains one or more sequence elements which direct its destination within the cell and may require proteolytic processing to become active. The term is often used for proteins translated with an N‑terminal targeting sequence (a presequence) and, in some cases, an additional propeptide that is removed during maturation. Together, these regions guide the protein to its correct compartment and regulate activation.

In prokaryotes and in the secretory pathways of eukaryotes, preproteins commonly carry an N‑terminal signal peptide that directs export via the Sec or Tat pathways and directs the protein into the endoplasmic reticulum or across the plasma membrane. The signal peptide is usually cleaved by signal peptidase to yield a mature, secreted or periplasmic protein. Many preproteins also contain propeptides that assist in folding or prevent premature activity and are removed by specific proteases to form the active protein.

In eukaryotic cells, some proteins are synthesized as preproproteins, where the presequence targets the ribosome–ER complex and the signal peptide is removed in the ER to form a proprotein. Further proteolytic processing, often by proprotein convertases, generates the mature, active protein. A well-known example is preproinsulin, which is processed to proinsulin in the ER and finally to insulin.

Targeting sequences also direct proteins to mitochondria or chloroplasts, where distinct processing steps produce the mature polypeptide. Overall, preproteins serve as precursors that ensure correct localization, folding, and timely activation of proteins.