Abstract:
: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.
journal_name
Proc Natl Acad Sci U S Aauthors
Groll M,Larionov OV,Huber R,de Meijere Adoi
10.1073/pnas.0600647103keywords:
subject
Has Abstractpub_date
2006-03-21 00:00:00pages
4576-9issue
12eissn
0027-8424issn
1091-6490pii
0600647103journal_volume
103pub_type
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