title: The nature and importance of the inter-epsilon chain disulfide bonds in human IgE.
abstract: IgE antibodies are best known for their pathological role in allergy. The class-specific effector sites are located in the epsilon chains; these form covalent dimers via two cystine residues (Cys241 and Cys328) linking opposite C epsilon 2 domains. The nature and biological significance of the inter-epsilon chain disulfide-bond arrangement is unresolved. For structural and functional analysis site-specific mutations were introduced into the C epsilon 2 domain of recombinant human IgE. The introduction of an additional cyanogen bromide cleavage site (His246----Met) facilitated the identification of parallel disulfide bond pairing. This linkage was also confirmed for myeloma IgE PS by sequence determination of disulfide-linked C epsilon 2 dimers. Substitution of Cys241 and Cys328 by Ser does not destroy receptor binding, but reductive alkylation, or the replacement of Cys328 by Met, leads to loss of activity. This shows that covalent dimerization is not essential for IgE/receptor interaction and points to the importance of the structural integrity of the site surrounding Cys328, visualized in a new model of human Fc epsilon.
authors.affiliation: Krebs Institute for Biomolecular Research, Department of Molecular Biology and Biotechnology, University of Sheffield, GB.
authors.forename: B A
authors.initials: BA
authors.lastname: Helm
authors.forename: Y
authors.initials: Y
authors.lastname: Ling
authors.forename: C
authors.initials: C
authors.lastname: Teale
authors.forename: E A
authors.initials: EA
authors.lastname: Padlan
authors.forename: M
authors.initials: M
authors.lastname: Brüggemann
mesh_terms: D000595:Amino Acid Sequence; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D004220:Disulfides; D006801:Humans; D007073:Immunoglobulin E / Q000737:chemistry* / Q000502:physiology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011961:Receptors, Fc / Q000378:metabolism; D017455:Receptors, IgE; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D004220:Disulfides; D011961:Receptors, Fc; D017455:Receptors, IgE; D011994:Recombinant Proteins; D007073:Immunoglobulin E