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Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cells

The transporter associated with antigen processing (TAP) is a key element of the major histocompatibility complex (MHC) class I antigen processing and presentation pathway. Nonfunctional TAP complexes impair the translocation of cytosol-derived proteolytic peptides to the endoplasmic reticulum lumen...

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Autores principales: Martín-Galiano, Antonio J., López, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333353/
https://www.ncbi.nlm.nih.gov/pubmed/30645615
http://dx.doi.org/10.1371/journal.pone.0210583
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author Martín-Galiano, Antonio J.
López, Daniel
author_facet Martín-Galiano, Antonio J.
López, Daniel
author_sort Martín-Galiano, Antonio J.
collection PubMed
description The transporter associated with antigen processing (TAP) is a key element of the major histocompatibility complex (MHC) class I antigen processing and presentation pathway. Nonfunctional TAP complexes impair the translocation of cytosol-derived proteolytic peptides to the endoplasmic reticulum lumen. This drastic reduction in the available peptide repertoire leads to a significant decrease in MHC class I cell surface expression. Using mass spectrometry, different studies have analyzed the cellular MHC class I ligandome from TAP-deficient cells, but the analysis of the parental proteins, the source of these ligands, still deserves an in-depth analysis. In the present report, several bioinformatics protocols were applied to investigate the nature of parental proteins for the previously identified TAP-independent MHC class I ligands. Antigen processing in TAP-deficient cells mainly focused on small, abundant or highly integral transmembrane proteins of the cellular proteome. This process involved abundant proteins of the central RNA metabolism. In addition, TAP-independent ligands were preferentially cleaved from the N- and C-terminal ends with respect to the central regions of the parental proteins. The abundance of glycine, proline and aromatic residues in the C-terminal sequences from TAP-independently processed proteins allows the accessibility and specificity required for the proteolytic activities that generates the TAP-independent ligandome. This limited proteolytic activity towards a set of preferred proteins in a TAP-negative environment would therefore suffice to promote the survival of TAP-deficient individuals.
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spelling pubmed-63333532019-01-31 Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cells Martín-Galiano, Antonio J. López, Daniel PLoS One Research Article The transporter associated with antigen processing (TAP) is a key element of the major histocompatibility complex (MHC) class I antigen processing and presentation pathway. Nonfunctional TAP complexes impair the translocation of cytosol-derived proteolytic peptides to the endoplasmic reticulum lumen. This drastic reduction in the available peptide repertoire leads to a significant decrease in MHC class I cell surface expression. Using mass spectrometry, different studies have analyzed the cellular MHC class I ligandome from TAP-deficient cells, but the analysis of the parental proteins, the source of these ligands, still deserves an in-depth analysis. In the present report, several bioinformatics protocols were applied to investigate the nature of parental proteins for the previously identified TAP-independent MHC class I ligands. Antigen processing in TAP-deficient cells mainly focused on small, abundant or highly integral transmembrane proteins of the cellular proteome. This process involved abundant proteins of the central RNA metabolism. In addition, TAP-independent ligands were preferentially cleaved from the N- and C-terminal ends with respect to the central regions of the parental proteins. The abundance of glycine, proline and aromatic residues in the C-terminal sequences from TAP-independently processed proteins allows the accessibility and specificity required for the proteolytic activities that generates the TAP-independent ligandome. This limited proteolytic activity towards a set of preferred proteins in a TAP-negative environment would therefore suffice to promote the survival of TAP-deficient individuals. Public Library of Science 2019-01-15 /pmc/articles/PMC6333353/ /pubmed/30645615 http://dx.doi.org/10.1371/journal.pone.0210583 Text en © 2019 Martín-Galiano, López http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Martín-Galiano, Antonio J.
López, Daniel
Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cells
title Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cells
title_full Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cells
title_fullStr Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cells
title_full_unstemmed Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cells
title_short Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cells
title_sort computational characterization of the peptidome in transporter associated with antigen processing (tap)-deficient cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6333353/
https://www.ncbi.nlm.nih.gov/pubmed/30645615
http://dx.doi.org/10.1371/journal.pone.0210583
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