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

被引:72
作者
Groll, M
Larionov, OV
Huber, R
de Meijere, A
机构
[1] Univ Munich, Adolf Butenandt Inst, D-81377 Munich, Germany
[2] Inst Organ & Biomol Chem, D-27077 Gottingen, Germany
[3] Max Planck Inst Biochem, D-82152 Martinsried, Germany
[4] Tech Univ Munich, D-85747 Garching, Germany
关键词
antigen presentation; IFN-gamma; inhibition;
D O I
10.1073/pnas.0600647103
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:4576 / 4579
页数:4
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