title: Structure of the human IgE-Fc C epsilon 3-C epsilon 4 reveals conformational flexibility in the antibody effector domains.
abstract: IgE antibodies mediate antiparasitic immune responses and the inflammatory reactions of allergy and asthma. We have solved the crystal structure of the human IgE-Fc Cepsilon3-Cepsilon4 domains to 2.3 A resolution. The structure reveals a large rearrangement of the N-terminal Cepsilon3 domains when compared to related IgG-Fc structures and to the IgE-Fc bound to its high-affinity receptor, FcepsilonRI. The IgE-Fc adopts a more compact, closed configuration that places the two Cepsilon3 domains in close proximity, decreases the size of the interdomain cavity, and obscures part of the FcepsilonRI binding site. IgE-Fc conformational flexibility may be required for interactions with two distinct IgE receptors, and the structure suggests strategies for the design of therapeutic compounds for the treatment of IgE-mediated diseases.
authors.affiliation: Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: B A
authors.initials: BA
authors.lastname: Wurzburg
authors.forename: S C
authors.initials: SC
authors.lastname: Garman
authors.forename: T S
authors.initials: TS
authors.lastname: Jardetzky
mesh_terms: D000918:Antibody Specificity; D001666:Binding Sites, Antibody; D002236:Carbohydrate Conformation; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004187:Disaccharides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007127:Immunoglobulin Constant Regions / Q000737:chemistry* / Q000378:metabolism; D007073:Immunoglobulin E / Q000737:chemistry* / Q000378:metabolism; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D009844:Oligosaccharides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017455:Receptors, IgE / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D004187:Disaccharides; D007127:Immunoglobulin Constant Regions; D007141:Immunoglobulin Fc Fragments; D009844:Oligosaccharides; D017455:Receptors, IgE; D007073:Immunoglobulin E