Diversity of proteasomal missions: fine tuning of the immune response.
The majority of cellular proteins are degraded by proteasomes within the ubiquitin-proteasome ATP-dependent degradation pathway. Products of proteasomal activity are short peptides that are further hydrolysed by proteases to single amino acids. However, some peptides can escape this degradation, being selected and taken up by major histocompatibility complex (MHC) class I molecules for presentation to the immune system on the cell surface. MHC class I molecules are highly selective and specific in terms of ligand binding. Variability of peptides produced in living cells arises in a variety of ways, ensuring fast and efficient immune responses. Substitution of constitutive proteasomal subunits with immunosubunits leads to conformational changes in the substrate binding channels, resulting in a modified protein cleavage pattern and consequently in the generation of new antigenic peptides. The recently discovered event of proteasomal peptide splicing opens new horizons in the understanding of additional functions that proteasomes apparently possess. Whether peptide splicing is an occasional side product of proteasomal activity still needs to be clarified. Both gamma-interferon-induced immunoproteasomes and peptide splicing represent two significant events providing increased diversity of antigenic peptides for flexible and fine-tuned immune response.
Borissenko
Ljudmila
L
Charité (CCM), Institut für Biochemie, AG Strukturforschung, Monbijoustrasse 2, D-10117 Berlin, Germany.
Groll
Michael
M
D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology / Q000378:metabolism*; D047669:Exteins / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism*; D047668:Inteins / Q000502:physiology; D010447:Peptide Hydrolases / Q000276:immunology / Q000378:metabolism*; D010455:Peptides / Q000276:immunology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000276:immunology / Q000378:metabolism*; D019154:Protein Splicing; D014452:Ubiquitins / Q000276:immunology / Q000378:metabolism*
D000941:Antigens; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D014452:Ubiquitins; D010447:Peptide Hydrolases; D046988:Proteasome Endopeptidase Complex