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

Proceedings of the National Academy of Sciences of the United States of America
Michael GrollArmin de Meijere

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.

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Citations

Oct 22, 2008·Journal of the American Chemical Society·Michael GrollEric N Jacobsen
Aug 19, 2007·Biological Chemistry·Ljudmila Borissenko, Michael Groll
Jan 8, 2016·Annual Review of Pharmacology and Toxicology·Paweł Śledź, Wolfgang Baumeister
Jul 29, 2008·Current Opinion in Chemical Biology·Bradley S MooreRyan P McGlinchey
Dec 26, 2008·Journal of Peptide Science : an Official Publication of the European Peptide Society·Michael GrollLuis Moroder
Mar 4, 2014·Medicinal Research Reviews·Nicola MicaleMaria Zappalà
Mar 29, 2014·Journal of Peptide Science : an Official Publication of the European Peptide Society·Mauro MarastoniRiccardo Gavioli
Jul 10, 2010·Biochimie·Geoffroy de Bettignies, Olivier Coux
Jan 31, 2012·Chemistry & Biology·Alexei F KisselevHerman S Overkleeft
Sep 20, 2008·Bioorganic & Medicinal Chemistry Letters·Makoto HasegawaTamio Mizukami
Jun 29, 2017·Journal of Enzyme Inhibition and Medicinal Chemistry·Mauro MarastoniDelia Preti
Aug 5, 2014·ChemMedChem·Constantin VossBoris Schmidt
Mar 12, 2016·Nature Communications·Eva M HuberMichael Groll
Apr 29, 2009·Expert Opinion on Therapeutic Targets·Sachiko Tsukamoto, Hideyoshi Yokosawa
Nov 1, 2011·Chemical Communications : Chem Comm·Melissa Ann Gräwert, Michael Groll
Jan 31, 2015·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alexey BelogurovAlexander Gabibov
Sep 6, 2011·Organic & Biomolecular Chemistry·Sylvain AubryDavid Crich
Jun 28, 2012·Organic & Biomolecular Chemistry·Armin de MeijereMazen Es-Sayed
Aug 30, 2013·Organic & Biomolecular Chemistry·Shuhei KawamuraSatoshi Shuto
May 15, 2015·Angewandte Chemie·Michael GrollAntje Ludwig
Sep 29, 2011·Organic & Biomolecular Chemistry·Vadim S KorotkovArmin de Meijere
Apr 30, 2017·Angewandte Chemie·Felix WolfLeonard Kaysser
Aug 29, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Benoît GuillaumeBenoît J Van den Eynde
Feb 28, 2021·European Journal of Medicinal Chemistry·Juan WangYan Xu
Feb 24, 2007·Chemical Reviews·Ljudmila Borissenko, Michael Groll
Oct 29, 2021·Journal of the American Chemical Society·Shotaro ShimoIkuro Abe

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