Tim14-Tim16 complex from S. cerevisiae

[43] Mokranjac D., Bourenkov G., Hell K., Neupert W., Groll M.
Structure and function of Tim14 and Tim16, the J and J-like components of the mitochondrial protein import motor
EMBO J., 2006, 25, 4675-85, PDF

Most class I MHC ligands are generated from the vast majority of cellular proteins by proteolysis within the ubiquitin-proteasome pathway and are presented on the cell surface by MHC class I molecules. Here, we present the crystallographic analysis of yeast 20S proteasome in complex with the inhibitor homobelactosin C. The structure reveals a unique inhibitor-binding mode and provides information about the composition of proteasomal primed substrate-binding sites. IFN-gamma inducible substitution of proteasomal constitutive subunits by immunosubunits modulates characteristics of generated peptides, thus producing fragments with higher preference for binding to MHC class I molecules. The structural data for the proteasome:homobelactosin C complex provide an explanation for involvement of immunosubunits in antigen generation and open perspectives for rational design of ligands, inhibiting exclusively constitutive proteasomes or immunoproteasomes.