Signaalpeptidase

Signaalpeptidase, or signal peptidase, is a family of intramembrane proteases that removes signal peptides from nascent proteins as they enter the secretory pathway. Signal peptides are short N-terminal sequences that direct proteins to the endoplasmic reticulum in eukaryotes or to the periplasm in bacteria. The cleavage by signaalpeptidase occurs at a defined site after the hydrophobic core of the signal sequence, releasing the mature protein and enabling proper folding and localization.

In bacteria, two main classes exist: signal peptidase I (SPase I), which processes most secreted and periplasmic proteins, and signal peptidase II (SPase II), which specializes in lipoproteins bearing a conserved lipobox motif. In eukaryotes and archaea, a dedicated signal peptidase complex resides in the endoplasmic reticulum membrane, with catalytic and auxiliary subunits that together execute processing of secretory and membrane proteins.

Localization and mechanism: Signaalpeptidases are integral membrane enzymes with active sites facing the lumen or periplasm. Cleavage typically occurs as proteins are targeted to the membrane and enter the secretory pathway, ensuring maturation before trafficking to their final destinations.

Significance: Signaalpeptidase activity is essential for maturation and proper localization of a large subset of secreted, periplasmic, and membrane proteins. Disruption of signal peptide removal can block protein maturation and affect cell viability.

Clinical and research notes: Bacterial signaalpeptidase inhibitors have been studied as potential antibiotics. In eukaryotes, defects in signal peptide processing can impair protein maturation and are of interest in cell biology and disease contexts.