SPase

SPase, or signal peptide peptidase, is a term used for a set of membrane-associated proteases that remove signal peptides from newly exported proteins, enabling maturation and proper localization. They are essential components of protein secretion pathways in bacteria, archaea, and eukaryotes.

Bacterial SPase I and SPase II function in distinct but related pathways. SPase I (often encoded by lepB) cleaves most secretory preproteins after their signal sequence, typically at an AXA motif near the cleavage site. It is an aspartyl protease embedded in the inner membrane with its active site facing the periplasm. SPase II (lspA) acts on prolipoproteins; after lipobox processing by Lgt and subsequent lipid modification, the signal peptide is removed and a lipid anchor is created. SPase II recognizes the lipobox motif and cuts just before the conserved cysteine that becomes lipid-modified. Globomycin is a known inhibitor of SPase II.

In eukaryotes, signal peptide peptidases (SPP and SPPL proteases) are intramembrane aspartyl proteases of the presenilin family. They reside in the endoplasmic reticulum and cleave signal peptides within the membrane after proteins are translocated into the ER, producing membrane-embedded peptide products that are degraded. SPP/SPPLs typically have multiple transmembrane helices and rely on catalytic aspartates in their protease core; they can also process other substrates and are implicated in protein quality control and antigen processing.

SPases are studied for their essential role in protein maturation and as potential targets in antibiotic development (notably SPase II inhibitors) and in the broader field of intramembrane proteolysis.