Inhibitor-binding mode of homobelactosin C to proteasomes: new insights into class I MHC ligand generation.

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.

authors

Groll M,Larionov OV,Huber R,de Meijere A

doi

10.1073/pnas.0600647103

keywords:

subject

Has Abstract

pub_date

2006-03-21 00:00:00

pages

4576-9

issue

12

eissn

0027-8424

issn

1091-6490

pii

0600647103

journal_volume

103

pub_type

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