The crystal structure of IgE Fc reveals an asymmetrically bent conformation

• Published in: Nature immunology Vol. 3; no. 7; pp. 681 - 686
• Main Authors: Sutton, Brian J, Wan, Tommy, Beavil, Rebecca L, Fabiane, Stella M, Beavil, Andrew J, Sohi, Maninder K, Keown, Maura, Young, Robert J, Henry, Alistair J, Owens, Ray J, Gould, Hannah J
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01-07-2002
• Subjects: Carbohydrate Conformation; Crystallography, X-Ray; Dimerization; Humans; Hypersensitivity; Immunoglobulin Constant Regions - chemistry; Immunoglobulin E - chemistry; Models, Molecular; Protein Structure, Tertiary; Receptors, IgE - chemistry
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni811

The distinguishing structural feature of immunoglobulin E (IgE), the antibody responsible for allergic hypersensitivity, is the C epsilon 2 domain pair that replaces the hinge region of IgG. The crystal structure of the IgE Fc (constant fragment) at a 2.6-A resolution has revealed these domains. They display a distinctive, disulfide-linked Ig domain interface and are folded back asymmetrically onto the C epsilon 3 and C epsilon 4 domains, which causes an acute bend in the IgE molecule. The structure implies that a substantial conformational change involving C epsilon 2 must accompany binding to the mast cell receptor Fc epsilon RI. This may be the basis of the exceptionally slow dissociation rate of the IgE-Fc epsilon RI complex and, thus, of the ability of IgE to cause persistent allergic sensitization of mast cells.