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dc.contributor.authorMartin-Galiano, Antonio Javier 
dc.contributor.authorLopez, Daniel
dc.identifier.citationPLoS One. 2019 Jan 15;14(1):e0210583.es_ES
dc.description.abstractThe 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.es_ES
dc.description.sponsorshipThis work was supported by the Spanish Ministry of Economy (MINECO/FEDER) grant SAF2014-58052 and Acción Estratégica en Salud 2019 to DL. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptes_ES
dc.publisherPublic Library of Science (PLOS) es_ES
dc.subject.meshATP-Binding Cassette Transporters es_ES
dc.subject.meshAntigen Presentation es_ES
dc.subject.meshAntigen-Presenting Cells es_ES
dc.subject.meshCD8-Positive T-Lymphocytes es_ES
dc.subject.meshComputational Biology es_ES
dc.subject.meshEndoplasmic Reticulum es_ES
dc.subject.meshHistocompatibility Antigens Class I es_ES
dc.subject.meshHumans es_ES
dc.subject.meshLigands es_ES
dc.subject.meshPeptides es_ES
dc.subject.meshProtein Transport es_ES
dc.subject.meshProteomics es_ES
dc.titleComputational characterization of the peptidome in transporter associated with antigen processing (TAP)-deficient cellses_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderMinisterio de Economía y Competitividad (España) 
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) 
dc.identifier.journalPloS onees_ES
dc.repisalud.centroISCIII::Centro Nacional de Microbiología::Unidades Comunes Científico-Técnicas (UCCT)::Unidad de Bioinformáticaes_ES
dc.rights.accessRightsopen accesses_ES

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Atribución 4.0 Internacional
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