Conformational changes in IgE contribute to its uniquely slow dissociation rate from receptor Fc[varepsilon]RI
Among antibody classes, IgE has a uniquely slow dissociation rate from, and high affinity for, its cell surface receptor Fc[varepsilon]RI. We show the structural basis for these key determinants of the ability of IgE to mediate allergic hypersensitivity through the 3.4-Å-resolution crystal structure...
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| Veröffentlicht in: | Nature structural & molecular biology 2011-05, Vol.18 (5), p.571 |
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| creator | Holdom, Mary D Davies, Anna M Nettleship, Joanne E Bagby, Sarah C Dhaliwal, Balvinder Girardi, Enrico Hunt, James Gould, Hannah J Beavil, Andrew J Mcdonnell, James M Owens, Ray J Sutton, Brian J |
| description | Among antibody classes, IgE has a uniquely slow dissociation rate from, and high affinity for, its cell surface receptor Fc[varepsilon]RI. We show the structural basis for these key determinants of the ability of IgE to mediate allergic hypersensitivity through the 3.4-Å-resolution crystal structure of human IgE-Fc (consisting of the C[varepsilon]2, C[varepsilon]3 and C[varepsilon]4 domains) bound to the extracellular domains of the Fc[varepsilon]RI α chain. Comparison with the structure of free IgE-Fc (reported here at a resolution of 1.9 Å) shows that the antibody, which has a compact, bent structure before receptor engagement, becomes even more acutely bent in the complex. Thermodynamic analysis indicates that the interaction is entropically driven, which explains how the noncontacting C[varepsilon]2 domains, in place of the flexible hinge region of IgG antibodies, contribute together with the conformational changes to the unique binding properties of IgE. [PUBLICATION ABSTRACT] |
| doi_str_mv | 10.1038/nsmb.2044 |
| format | Article |
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We show the structural basis for these key determinants of the ability of IgE to mediate allergic hypersensitivity through the 3.4-Å-resolution crystal structure of human IgE-Fc (consisting of the C[varepsilon]2, C[varepsilon]3 and C[varepsilon]4 domains) bound to the extracellular domains of the Fc[varepsilon]RI α chain. Comparison with the structure of free IgE-Fc (reported here at a resolution of 1.9 Å) shows that the antibody, which has a compact, bent structure before receptor engagement, becomes even more acutely bent in the complex. Thermodynamic analysis indicates that the interaction is entropically driven, which explains how the noncontacting C[varepsilon]2 domains, in place of the flexible hinge region of IgG antibodies, contribute together with the conformational changes to the unique binding properties of IgE. 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| subjects | Binding sites Cellular biology Crystal structure Hypersensitivity Immunoglobulins Molecular biology Proteins |
| title | Conformational changes in IgE contribute to its uniquely slow dissociation rate from receptor Fc[varepsilon]RI |
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