11S

11S, commonly referred to as the 11S regulator or PA28, is a proteasome regulatory complex that binds to the 20S proteasome core particle. By capping the 20S core, it modulates proteolysis and promotes the generation of peptide fragments that can be presented by MHC class I molecules. The 11S regulator is distinct from the 19S regulatory particle, which manages ubiquitin-tagged substrates and ATP-dependent unfolding.

Composition and forms: In vertebrates, the 11S regulator exists in two principal forms. The PA28αβ heteroheptamer, formed by subunits PA28α (PSME1) and PA28β (PSME2), is common in many tissues. PA28γ (PSME3) can form a homoheptamer and can associate with the proteasome under certain conditions. The 11S family in humans is encoded by PSME1, PSME2, and PSME3.

Function and mechanism: The 11S regulator accelerates degradation of short peptide substrates and enhances the generation of antigenic peptides for transport into the endoplasmic reticulum for loading onto MHC class I molecules. It generally supports ubiquitin-independent proteolysis and can modulate the proteasome’s peptidase activities, particularly the chymotrypsin-like activity.

Biological context: Expression of 11S regulator subunits is influenced by inflammatory signals such as interferon-γ, linking it to immune surveillance and antigen processing. Through its regulation of peptide generation, the 11S regulator contributes to the repertoire of peptides available for immune presentation and may impact various physiological and pathological processes.

See also: proteasome, PA28, immunoproteasome.