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A Peptide/MHCII conformer generated in the presence of exchange peptide is substrate for HLA-DM editing

The mechanism of HLA-DM (DM) activity is still unclear. We have shown that DM-mediated peptide release from HLA-DR (DR) is dependent on the presence of exchange peptide. However, DM also promotes a small amount of peptide release in the absence of exchange peptide. Here we show that SDS-PAGE separat...

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Detalles Bibliográficos
Autores principales: Ferrante, Andrea, Gorski, Jack
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338121/
https://www.ncbi.nlm.nih.gov/pubmed/22545194
http://dx.doi.org/10.1038/srep00386
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author Ferrante, Andrea
Gorski, Jack
author_facet Ferrante, Andrea
Gorski, Jack
author_sort Ferrante, Andrea
collection PubMed
description The mechanism of HLA-DM (DM) activity is still unclear. We have shown that DM-mediated peptide release from HLA-DR (DR) is dependent on the presence of exchange peptide. However, DM also promotes a small amount of peptide release in the absence of exchange peptide. Here we show that SDS-PAGE separates purified peptide/DR1 complexes (pDR1) into two conformers whose ratio is peptide K(d)-dependent. In the absence of exchange peptide, DM only releases peptide from the slower migrating conformer. Addition of exchange peptide converts the DM-resistant conformer to the slower migrating conformer, which is DM labile. Thus, exchange peptide generates a conformer of pDR1 which constitutes the intermediate for peptide exchange and the substrate for DM activity. The resolution of the intermediate favors the highest affinity peptide. However, once folded into the DM-resistant conformer, even low affinity peptides can be presented in the absence of free peptide, broadening the repertoire available for presentation.
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spelling pubmed-33381212012-04-27 A Peptide/MHCII conformer generated in the presence of exchange peptide is substrate for HLA-DM editing Ferrante, Andrea Gorski, Jack Sci Rep Article The mechanism of HLA-DM (DM) activity is still unclear. We have shown that DM-mediated peptide release from HLA-DR (DR) is dependent on the presence of exchange peptide. However, DM also promotes a small amount of peptide release in the absence of exchange peptide. Here we show that SDS-PAGE separates purified peptide/DR1 complexes (pDR1) into two conformers whose ratio is peptide K(d)-dependent. In the absence of exchange peptide, DM only releases peptide from the slower migrating conformer. Addition of exchange peptide converts the DM-resistant conformer to the slower migrating conformer, which is DM labile. Thus, exchange peptide generates a conformer of pDR1 which constitutes the intermediate for peptide exchange and the substrate for DM activity. The resolution of the intermediate favors the highest affinity peptide. However, once folded into the DM-resistant conformer, even low affinity peptides can be presented in the absence of free peptide, broadening the repertoire available for presentation. Nature Publishing Group 2012-04-27 /pmc/articles/PMC3338121/ /pubmed/22545194 http://dx.doi.org/10.1038/srep00386 Text en Copyright © 2012, Macmillan Publishers Limited. All rights reserved http://creativecommons.org/licenses/by-nc-sa/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareALike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Article
Ferrante, Andrea
Gorski, Jack
A Peptide/MHCII conformer generated in the presence of exchange peptide is substrate for HLA-DM editing
title A Peptide/MHCII conformer generated in the presence of exchange peptide is substrate for HLA-DM editing
title_full A Peptide/MHCII conformer generated in the presence of exchange peptide is substrate for HLA-DM editing
title_fullStr A Peptide/MHCII conformer generated in the presence of exchange peptide is substrate for HLA-DM editing
title_full_unstemmed A Peptide/MHCII conformer generated in the presence of exchange peptide is substrate for HLA-DM editing
title_short A Peptide/MHCII conformer generated in the presence of exchange peptide is substrate for HLA-DM editing
title_sort peptide/mhcii conformer generated in the presence of exchange peptide is substrate for hla-dm editing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3338121/
https://www.ncbi.nlm.nih.gov/pubmed/22545194
http://dx.doi.org/10.1038/srep00386
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