Structure of the human IgE-Fc C epsilon 3-C epsilon 4 reveals conformational flexibility in the antibody effector domains.
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.
Wurzburg
B A
BA
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
Garman
S C
SC
Jardetzky
T S
TS
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
D004187:Disaccharides; D007127:Immunoglobulin Constant Regions; D007141:Immunoglobulin Fc Fragments; D009844:Oligosaccharides; D017455:Receptors, IgE; D007073:Immunoglobulin E