Please use this identifier to cite or link to this item: https://olympias.lib.uoi.gr/jspui/handle/123456789/23984
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dc.contributor.authorEttinger, R. A.en
dc.contributor.authorPapadopoulos, G. K.en
dc.contributor.authorMoustakas, A. K.en
dc.contributor.authorNepom, G. T.en
dc.contributor.authorKwok, W. W.en
dc.date.accessioned2015-11-24T19:37:04Z-
dc.date.available2015-11-24T19:37:04Z-
dc.identifier.issn0022-1767-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/23984-
dc.rightsDefault Licence-
dc.subject*Allelesen
dc.subjectAmino Acid Motifsen
dc.subjectAutoantigens/metabolismen
dc.subjectBinding Sites/genetics/immunologyen
dc.subjectBiotin/analogs & derivatives/metabolismen
dc.subjectCell Line, Transformeden
dc.subjectDiabetes Mellitus, Type 1/*genetics/*immunologyen
dc.subject*Genetic Predisposition to Diseaseen
dc.subjectGenetic Variationen
dc.subjectGlutamate Decarboxylase/metabolismen
dc.subjectHLA-DQ Antigens/*genetics/metabolismen
dc.subjectHLA-DQ beta-Chainsen
dc.subjectHumansen
dc.subjectInsulin/analogs & derivatives/metabolismen
dc.subjectIsoenzymes/metabolismen
dc.subjectMembrane Glycoproteins/*genetics/metabolismen
dc.subjectMembrane Proteins/metabolismen
dc.subjectModels, Molecularen
dc.subjectPeptide Fragments/*genetics/*metabolismen
dc.subjectProinsulin/metabolismen
dc.subjectProtein Binding/genetics/immunologyen
dc.subjectProtein Structure, Tertiaryen
dc.subjectProtein Tyrosine Phosphatase, Non-Receptor Type 1en
dc.subjectProtein Tyrosine Phosphatases/metabolismen
dc.subjectReceptor-Like Protein Tyrosine Phosphatases, Class 8en
dc.titleAllelic variation in key peptide-binding pockets discriminates between closely related diabetes-protective and diabetes-susceptible HLA-DQB1*06 allelesen
heal.typejournalArticle-
heal.type.enJournal articleen
heal.type.elΆρθρο Περιοδικούel
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/16424231-
heal.identifier.secondaryhttp://www.jimmunol.org/content/176/3/1988.full.pdf-
heal.languageen-
heal.accesscampus-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.publicationDate2006-
heal.abstractHLA-DQA1*0102-DQB1*0602 is associated with protection against type 1 diabetes (T1D). A similar allele, HLA-DQA1*0102-DQB1*0604, contributes to T1D susceptibility in certain populations but differs only at seven amino acids from HLA-DQA1*0102-DQB1*0602. Five of these polymorphisms are found within the peptide-binding groove, suggesting that differences in peptide binding contribute to the mechanism of their association with T1D. In this study, we determine the peptide-binding motif for HLA-DQA1*0102-DQB1*0604 allelic protein (DQ0604) in comparison to the established HLA-DQA1*0102-DQB1*0602 (DQ0602) motif using binding assays with model peptides from T1D autoantigens and homology modeling using the coordinates of the DQ0602-hypocretin 1-13 crystal structure. The peptide binding preferences were deduced with a peptide from insulin that bound both with a 2- to 3-fold difference in avidity using the same amino acids in the peptide as anchors. Peptide binding differences directly influenced by the polymorphisms in or nearby pockets 1, 6, and 9 were observed. In pocket 1, DQ0604 was better able to accommodate aromatic residues due to the beta86 and beta87 polymorphisms. A negatively charged amino acid was preferred by DQ0604 in pocket 6 due to the positively charged beta30His. In pocket 9, DQ0604 preferred aromatic amino acids due to the beta9 and beta30 polymorphisms and had low tolerance of acidic residues. beta57Val in DQ0604 functions differently than beta57Ala, in that it pushes alpha76Arg outside of the pocket, preventing the formation of a salt bridge with an acidic amino acid in the peptide. This study furthers our understanding of the structure-function relationships of MHC class II polymorphisms.en
heal.journalNameJ Immunolen
heal.journalTypepeer-reviewed-
heal.fullTextAvailabilityTRUE-
Appears in Collections:Άρθρα σε επιστημονικά περιοδικά ( Ανοικτά) - ΙΑΤ

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