THE NATURE AND IMPORTANCE OF THE INTER-EPSILON CHAIN DISULFIDE BONDS IN HUMAN IGE

被引:43
作者
HELM, BA
LING, Y
TEALE, C
PADLAN, EA
BRUGGEMANN, M
机构
[1] INST ANIM PHYSIOL & GENET RES,DEPT MOLEC EMBRYOL,CAMBRIDGE RES STN,CAMBRIDGE,ENGLAND
[2] NIADDKD,MOLEC BIOL LAB,BETHESDA,MD 20892
关键词
D O I
10.1002/eji.1830210631
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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页码:1543 / 1548
页数:6
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