Signal peptidase is an enzyme that plays a role in protein maturation. It targets and precisely removes specific short amino acid sequences, called signal peptides, found at the beginning of newly made proteins. This removal allows proteins to achieve their final functional shapes and be directed to their correct locations within or outside the cell.
The Journey of Proteins
Proteins are long chains of amino acids, assembled by ribosomes in the cell’s cytoplasm. Many are destined for internal compartments, secretion, or cellular membranes. To reach these destinations, they carry a signal sequence at their N-terminus. This sequence acts like a cellular address label, guiding the protein to the correct machinery.
As the signal peptide emerges from the ribosome, it is recognized by the signal recognition particle (SRP). This binding temporarily pauses protein synthesis and guides the ribosome-SRP complex to the endoplasmic reticulum (ER) membrane in eukaryotes, or the plasma membrane in prokaryotes. There, the complex docks with an SRP receptor, and the protein chain transfers to a translocon, allowing it to move across or into the membrane.
How Signal Peptidase Functions
Once the protein moves through the translocon into the endoplasmic reticulum lumen or membrane, signal peptidase becomes active. This enzyme identifies a specific cleavage site within the signal peptide, located between the signal peptide and the mature protein sequence. Signal peptidases are serine proteases, using a serine amino acid in their active site for cleavage. The active site of eukaryotic signal peptidase is positioned on the extracytoplasmic side of the membrane, facing the ER lumen.
Cleavage involves the hydrolysis of a peptide bond, removing the signal peptide. This specific action ensures the mature protein folds correctly and performs its designated function.
Types of Signal Peptidases
There are different types of signal peptidases, categorized by their substrates and cellular locations. Type I signal peptidases, found in both prokaryotes and eukaryotes, process proteins for secretion or membrane insertion. Type II signal peptidases are found in prokaryotes and process lipoproteins, while Type III signal peptidases occur in gram-negative bacteria, handling outer membrane proteins.
Why Signal Peptidase Matters
The precise action of signal peptidase is important for cellular life and protein function. By removing the signal peptide, the enzyme allows the newly synthesized protein to fold into its correct three-dimensional structure. This folding is necessary for the protein to become active and interact with other molecules or structures within the cell. Without this cleavage, many proteins would remain improperly localized or folded, rendering them non-functional.
Proper signal peptidase functioning ensures secreted proteins leave the cell and membrane proteins integrate correctly into their membranes. After cleavage, the discarded signal peptide is degraded within the cell, preventing its accumulation. A malfunction in signal peptidase activity can lead to cellular problems, disrupting protein secretion pathways and the biogenesis of membrane components.