Cutting Edge: Coding single nucleotide polymorphisms of endoplasmic reticulum aminopeptidase 1 can affect antigenic peptide generation in vitro by influencing basic enzymatic properties of the enzyme

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dc.contributor.authorEvnouchidou, I.en
dc.contributor.authorKamal, R. P.en
dc.contributor.authorSeregin, S. S.en
dc.contributor.authorGoto, Y.en
dc.contributor.authorTsujimoto, M.en
dc.contributor.authorHattori, A.en
dc.contributor.authorVoulgari, P. V.en
dc.contributor.authorDrosos, A. A.en
dc.contributor.authorAmalfitano, A.en
dc.contributor.authorYork, I. A.en
dc.contributor.authorStratikos, E.en
dc.date.accessioned2015-11-24T19:25:50Z
dc.date.available2015-11-24T19:25:50Z
dc.identifier.issn1550-6606-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/22660
dc.rightsDefault Licence-
dc.subject5' Untranslated Regions/immunologyen
dc.subjectAllelesen
dc.subjectAmino Acid Substitution/geneticsen
dc.subjectAminopeptidases/*genetics/metabolism/physiologyen
dc.subjectAntigen Presentation/geneticsen
dc.subjectAntigens/*biosynthesisen
dc.subjectArginine/geneticsen
dc.subjectCell Lineen
dc.subjectEndoplasmic Reticulum/*enzymology/genetics/*immunologyen
dc.subjectGlutamine/geneticsen
dc.subjectHLA-A Antigens/genetics/metabolismen
dc.subjectHLA-B27 Antigen/metabolismen
dc.subjectHeLa Cellsen
dc.subjectHumansen
dc.subjectLysine/geneticsen
dc.subjectPeptide Biosynthesis/*genetics/immunologyen
dc.subjectPeptide Fragments/genetics/metabolismen
dc.subjectPolymorphism, Single Nucleotide/*immunologyen
dc.subjectSubstrate Specificity/geneticsen
dc.titleCutting Edge: Coding single nucleotide polymorphisms of endoplasmic reticulum aminopeptidase 1 can affect antigenic peptide generation in vitro by influencing basic enzymatic properties of the enzymeen
heal.abstractER aminopeptidase 1 (ERAP1) customizes antigenic peptide precursors for MHC class I presentation and edits the antigenic peptide repertoire. Coding single nucleotide polymorphisms (SNPs) in ERAP1 were recently linked with predisposition to autoimmune disease, suggesting a link between pathogenesis of autoimmunity and ERAP1-mediated Ag processing. To investigate this possibility, we analyzed the effect that disease-linked SNPs have on Ag processing by ERAP1 in vitro. Michaelis-Menten analysis revealed that the presence of SNPs affects the Michaelis constant and turnover number of the enzyme. Strikingly, specific ERAP1 allele-substrate combinations deviate from standard Michaelis-Menten behavior, demonstrating substrate-inhibition kinetics; to our knowledge, this phenomenon has not been described for this enzyme. Cell-based Ag-presentation analysis was consistent with changes in the substrate inhibition constant K(i), further supporting that ERAP1 allelic composition may affect Ag processing in vivo. We propose that these phenomena should be taken into account when evaluating the possible link between Ag processing and autoimmunity.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.primary10.4049/jimmunol.1003337-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/21242517-
heal.identifier.secondaryhttp://www.jimmunol.org/content/186/4/1909.full.pdf-
heal.journalNameJ Immunolen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate2011-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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