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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Detalles Bibliográficos
Autores: Martin-Galiano, Antonio Javier, Lopez, Daniel
Tipo de recurso: artículo
Fecha de publicación:2019
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/8692
Acceso en línea:http://hdl.handle.net/20.500.12105/8692
Access Level:acceso abierto
Palabra clave:ATP-Binding Cassette Transporters
Antigen Presentation
Antigen-Presenting Cells
CD8-Positive T-Lymphocytes
Computational Biology
Endoplasmic Reticulum
Histocompatibility Antigens Class I
Humans
Ligands
Peptides
Protein Transport
Proteomics
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spelling Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cellsMartin-Galiano, Antonio JavierLopez, DanielATP-Binding Cassette TransportersAntigen PresentationAntigen-Presenting CellsCD8-Positive T-LymphocytesComputational BiologyEndoplasmic ReticulumHistocompatibility Antigens Class IHumansLigandsPeptidesProtein TransportProteomicsThe 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 (PLOS)Ministerio de Economía y Competitividad (España)Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)20192019-11-2520192019-01-0120192019-01-01research articlehttp://purl.org/coar/resource_type/c_2df8fbb1VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/8692reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)InglésengES SAF2014-58052 Not availableopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/86922026-06-12T12:43:37Z
dc.title.none.fl_str_mv 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
spellingShingle Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cells
Martin-Galiano, Antonio Javier
ATP-Binding Cassette Transporters
Antigen Presentation
Antigen-Presenting Cells
CD8-Positive T-Lymphocytes
Computational Biology
Endoplasmic Reticulum
Histocompatibility Antigens Class I
Humans
Ligands
Peptides
Protein Transport
Proteomics
title_short 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_sort Computational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cells
dc.creator.none.fl_str_mv Martin-Galiano, Antonio Javier
Lopez, Daniel
author Martin-Galiano, Antonio Javier
author_facet Martin-Galiano, Antonio Javier
Lopez, Daniel
author_role author
author2 Lopez, Daniel
author2_role author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
dc.subject.none.fl_str_mv ATP-Binding Cassette Transporters
Antigen Presentation
Antigen-Presenting Cells
CD8-Positive T-Lymphocytes
Computational Biology
Endoplasmic Reticulum
Histocompatibility Antigens Class I
Humans
Ligands
Peptides
Protein Transport
Proteomics
topic ATP-Binding Cassette Transporters
Antigen Presentation
Antigen-Presenting Cells
CD8-Positive T-Lymphocytes
Computational Biology
Endoplasmic Reticulum
Histocompatibility Antigens Class I
Humans
Ligands
Peptides
Protein Transport
Proteomics
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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-11-25
2019
2019-01-01
2019
2019-01-01
dc.type.none.fl_str_mv research article
http://purl.org/coar/resource_type/c_2df8fbb1
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/8692
url http://hdl.handle.net/20.500.12105/8692
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv ES SAF2014-58052 Not available
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 4.0 Internacional
http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLOS)
publisher.none.fl_str_mv Public Library of Science (PLOS)
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.198674

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