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Fast peptide exchange on major histocompatibility complex class I molecules by acidic stabilization of a peptide‐empty intermediate
The cell biology and biochemistry of peptide exchange on major histocompatibility complex class I (MHC‐I) proteins are of great interest in the study of immunodominance, which requires iterative optimization of peptide affinity, and cross‐presentation of pathogen and tumor antigens, in which endogen...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley & Sons, Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9669992/ https://www.ncbi.nlm.nih.gov/pubmed/36258668 http://dx.doi.org/10.1002/pro.4478 |
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author | Saikia, Ankur Hadeler, Andries Prasad, Pranathi Zacharias, Martin Springer, Sebastian |
author_facet | Saikia, Ankur Hadeler, Andries Prasad, Pranathi Zacharias, Martin Springer, Sebastian |
author_sort | Saikia, Ankur |
collection | PubMed |
description | The cell biology and biochemistry of peptide exchange on major histocompatibility complex class I (MHC‐I) proteins are of great interest in the study of immunodominance, which requires iterative optimization of peptide affinity, and cross‐presentation of pathogen and tumor antigens, in which endogenous peptides are exchanged for exogenous ones. Even though several methods exist to catalyze peptide exchange on recombinant MHC‐I proteins, the cellular conditions and mechanisms allowing for peptide exchange in vivo remain unclear. Here, we demonstrate that low pH, as present in endosomes, indeed triggers peptide exchange, and we dissect the individual steps of the exchange reaction. We find that low pH stabilizes the peptide‐empty forms of MHC‐I that occur as intermediates of the exchange reaction, and that is synergizes with dipeptides and with disulfide‐mediated stabilization of MHC‐I. |
format | Online Article Text |
id | pubmed-9669992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley & Sons, Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-96699922022-12-01 Fast peptide exchange on major histocompatibility complex class I molecules by acidic stabilization of a peptide‐empty intermediate Saikia, Ankur Hadeler, Andries Prasad, Pranathi Zacharias, Martin Springer, Sebastian Protein Sci Full‐length Papers The cell biology and biochemistry of peptide exchange on major histocompatibility complex class I (MHC‐I) proteins are of great interest in the study of immunodominance, which requires iterative optimization of peptide affinity, and cross‐presentation of pathogen and tumor antigens, in which endogenous peptides are exchanged for exogenous ones. Even though several methods exist to catalyze peptide exchange on recombinant MHC‐I proteins, the cellular conditions and mechanisms allowing for peptide exchange in vivo remain unclear. Here, we demonstrate that low pH, as present in endosomes, indeed triggers peptide exchange, and we dissect the individual steps of the exchange reaction. We find that low pH stabilizes the peptide‐empty forms of MHC‐I that occur as intermediates of the exchange reaction, and that is synergizes with dipeptides and with disulfide‐mediated stabilization of MHC‐I. John Wiley & Sons, Inc. 2022-12 /pmc/articles/PMC9669992/ /pubmed/36258668 http://dx.doi.org/10.1002/pro.4478 Text en © 2022 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Full‐length Papers Saikia, Ankur Hadeler, Andries Prasad, Pranathi Zacharias, Martin Springer, Sebastian Fast peptide exchange on major histocompatibility complex class I molecules by acidic stabilization of a peptide‐empty intermediate |
title | Fast peptide exchange on major histocompatibility complex class I molecules by acidic stabilization of a peptide‐empty intermediate |
title_full | Fast peptide exchange on major histocompatibility complex class I molecules by acidic stabilization of a peptide‐empty intermediate |
title_fullStr | Fast peptide exchange on major histocompatibility complex class I molecules by acidic stabilization of a peptide‐empty intermediate |
title_full_unstemmed | Fast peptide exchange on major histocompatibility complex class I molecules by acidic stabilization of a peptide‐empty intermediate |
title_short | Fast peptide exchange on major histocompatibility complex class I molecules by acidic stabilization of a peptide‐empty intermediate |
title_sort | fast peptide exchange on major histocompatibility complex class i molecules by acidic stabilization of a peptide‐empty intermediate |
topic | Full‐length Papers |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9669992/ https://www.ncbi.nlm.nih.gov/pubmed/36258668 http://dx.doi.org/10.1002/pro.4478 |
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