Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/9149
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dc.contributor.authorHulett, M Den
dc.contributor.authorBrinkworth, R Ien
dc.contributor.authorMcKenzie, Ian F Cen
dc.contributor.authorHogarth, P Marken
dc.date.accessioned2015-05-15T22:07:36Z
dc.date.available2015-05-15T22:07:36Z
dc.date.issued1999-05-07en
dc.identifier.citationThe Journal of Biological Chemistry; 274(19): 13345-52en
dc.identifier.govdoc10224096en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/9149en
dc.description.abstractThe high affinity receptor for IgE (FcepsilonRI) plays an integral role in triggering IgE-mediated hypersensitivity reactions. The IgE-interactive site of human FcepsilonRI has previously been broadly mapped to several large regions in the second extracellular domain (D2) of the alpha-subunit (FcepsilonRIalpha). In this study, the IgE binding site of human FcepsilonRIalpha has been further localized to subregions of D2, and key residues putatively involved in the interaction with IgE have been identified. Chimeric receptors generated between FcepsilonRIalpha and the functionally distinct but structurally homologous low affinity receptor for IgG (FcgammaRIIa) have been used to localize two IgE binding regions of FcepsilonRIalpha to amino acid segments Tyr129-His134 and Lys154-Glu161. Both regions were capable of independently binding IgE upon placement into FcgammaRIIa. Molecular modeling of the three-dimensional structure of FcepsilonRIalpha-D2 has suggested that these binding regions correspond to the "exposed" C'-E and F-G loop regions at the membrane distal portion of the domain. A systematic site-directed mutagenesis strategy, whereby each residue in the Tyr129-His134 and Lys154-Glu161 regions of FcepsilonRIalpha was replaced with alanine, has identified key residues putatively involved in the interaction with IgE. Substitution of Tyr131, Glu132, Val155, and Asp159 decreased the binding of IgE, whereas substitution of Trp130, Trp156, Tyr160, and Glu161 increased binding. In addition, mutagenesis of residues Trp113, Val115, and Tyr116 in the B-C loop region, which lies adjacent to the C'-E and F-G loops, has suggested Trp113 also contributes to IgE binding, since the substitution of this residue with alanine dramatically reduces binding. This information should prove valuable in the design of strategies to intervene in the FcepsilonRIalpha-IgE interaction for the possible treatment of IgE-mediated allergic disease.en
dc.language.isoenen
dc.subject.otherAnimalsen
dc.subject.otherBinding Sitesen
dc.subject.otherCOS Cellsen
dc.subject.otherHumansen
dc.subject.otherImmunoglobulin E.metabolismen
dc.subject.otherModels, Molecularen
dc.subject.otherProtein Bindingen
dc.subject.otherReceptors, IgE.chemistry.metabolismen
dc.subject.otherRecombinant Proteins.chemistry.metabolismen
dc.titleFine structure analysis of interaction of FcepsilonRI with IgE.en
dc.typeJournal Articleen
dc.identifier.journaltitleThe Journal of biological chemistryen
dc.identifier.affiliationThe Austin Research Institute, Austin Hospital, Studley Road, Heidelberg, Victoria 3084, Australiaen
dc.description.pages13345-52en
dc.relation.urlhttps://pubmed.ncbi.nlm.nih.gov/10224096en
dc.type.austinJournal Articleen
item.openairetypeJournal Article-
item.fulltextNo Fulltext-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextnone-
item.cerifentitytypePublications-
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