Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/75223
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Título: | The origin of proteasome-inhibitor resistant HLA class I peptidomes: a study with HLA-A*68:01. |
Autor: | García-Medel, Noel CSIC; Sanz-Bravo, Alejandro CSIC ORCID; Barnea, Eilon; Admon, Arie; López de Castro, José A. CSIC | Palabras clave: | Peptidomes Proteasome-inhibitor In vivo Histocompatibility |
Fecha de publicación: | 2011 | Editor: | American Society for Biochemistry and Molecular Biology | Citación: | Molecular and Cellular Proteomics 11: (2012) | Resumen: | Some HLA class I molecules bind a significant fraction of their constitutive peptidomes in the presence of proteasome inhibitors. In this study, A*68:01-bound peptides, and their parental proteins, were characterized through massive mass spectrometry sequencing to refine its binding motif, including the nearly exclusive preference for C-terminal basic residues. Stable isotope tagging was used to distinguish proteasome-inhibitor sensitive and resistant ligands. The latter accounted for less than 20% of the peptidome and, like in HLA-B27, arose predominantly from small and basic proteins. Under the conditions used for proteasome inhibition in vivo, epoxomicin and MG-132 incompletely inhibited the hydrolysis of fluorogenic substrates specific for the tryptic or for both the tryptic and chymotryptic subspecificities, respectively. This incomplete inhibition was also reflected in the cleavage of synthetic peptide precursors of A*68:01 ligands. For these substrates, the inhibition of the proteasome resulted in altered cleavage patterns. However these alterations did not upset the balance between cleavage at peptide bonds resulting in epitope destruction and those leading to their generation. The results indicate that inhibitor-resistant HLA class I ligands are not necessarily produced by non-proteasomal pathways. However, their generation is not simply explained by decreased epitope destruction upon incomplete proteasomal inhibition and may require additional proteolytic steps acting on incompletely processed proteasomal products. | Versión del editor: | http://dx.doi.org/10.1074/mcp.M111.011486 | URI: | http://hdl.handle.net/10261/75223 | DOI: | 10.1074/mcp.M111.011486 | ISSN: | 1535-9476 |
Aparece en las colecciones: | (CBM) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
10
checked on 13-abr-2024
SCOPUSTM
Citations
14
checked on 19-abr-2024
WEB OF SCIENCETM
Citations
10
checked on 26-feb-2024
Page view(s)
320
checked on 26-abr-2024
Download(s)
99
checked on 26-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
Artículos relacionados:
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.