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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2012
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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. |
format | Online Article Text |
id | pubmed-3338121 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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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