Cayanis E, Sarangarajan R, Lombes M, Nahon E, Edelman I S, Erlanger B F
Department of Microbiology, Columbia University, New York, NY 10032.
Proc Natl Acad Sci U S A. 1989 Apr;86(7):2138-42. doi: 10.1073/pnas.86.7.2138.
A monoclonal antibody (8G11-C6) generated by an auto-anti-idiotypic route and directed to a site near the ligand-binding site of the glucocorticoid receptor also binds to native insulin and the B chain of insulin but not to the A chain of insulin. The glucocorticoid receptor and the B chain of insulin, therefore, share a cross-reacting epitope. Examination of the primary sequences of the two proteins revealed a limited number of regions of identity or close homology. Several peptides representative of those regions were synthesized. A heptapeptide sequence of the B chain of insulin with homology to a sequence in the first "zinc finger" of the DNA-binding domain of the glucocorticoid receptor was identified as the cross-reactive epitope. This heptapeptide sequence is restricted to and highly conserved among insulins of various species. Homologous sequences are found in the DNA-binding domains of most steroid receptors and related DNA-binding proteins. Consistent with this is the finding that 8G11-C6 inhibits the binding of glucocorticoid receptor to DNA-cellulose.
通过自身抗独特型途径产生的、针对糖皮质激素受体配体结合位点附近位点的单克隆抗体（8G11-C6），也能与天然胰岛素及胰岛素B链结合，但不与胰岛素A链结合。因此，糖皮质激素受体与胰岛素B链具有交叉反应表位。对这两种蛋白质一级序列的研究揭示了数量有限的相同或高度同源区域。合成了代表这些区域的几种肽。胰岛素B链中与糖皮质激素受体DNA结合结构域第一个“锌指”中的序列具有同源性的七肽序列，被确定为交叉反应表位。该七肽序列在各种物种的胰岛素中是局限且高度保守的。在大多数类固醇受体和相关DNA结合蛋白的DNA结合结构域中也发现了同源序列。与此一致的是，8G11-C6可抑制糖皮质激素受体与DNA纤维素的结合。
