Braun T, Schofield P R, Sprengel R
Laboratory of Molecular Neuroendocrinology, University of Heidelberg, FRG.
EMBO J. 1991 Jul;10(7):1885-90. doi: 10.1002/j.1460-2075.1991.tb07714.x.
Recombinant expression of truncated receptors for luteinizing hormone/chorionic gonadotropin (LH/CG) revealed that the amino-terminal leucine-rich repeats 1-8 of the extracellular receptor domain bind human chorionic gonadotropin (hCG) with an affinity (Kd = 0.72 +/- 0.2 nM) similar to that of the native LH/CG receptor (Kd = 0.48 +/- 0.05 nM). LH/CG receptor leucine-rich repeats 1-8 were used to replace homologous sequences in the closely related receptor for follicle stimulating hormone (FSH). Cells expressing such chimeric LH/CG-FSH receptors bind hCG and show elevated cylic AMP levels when stimulated by hCG but not by recombinant human FSH (rhFSH). Similarly, a chimeric LH/CG receptor in which leucine-rich repeats 1-11 originated from the FSH receptor is activated by rhFSH but not by hCG. For this chimera, no residual [125I] hCG binding was observed in a range of 2 pM to 10 nM. Our results demonstrate that specificity of gonadotropin receptors is determined by a high affinity hormone binding site formed by the amino-terminal leucine-rich receptor repeats.
促黄体生成素/绒毛膜促性腺激素（LH/CG）截短型受体的重组表达表明，细胞外受体结构域的氨基末端富含亮氨酸重复序列1-8与人绒毛膜促性腺激素（hCG）结合的亲和力（Kd = 0.72 +/- 0.2 nM）与天然LH/CG受体的亲和力（Kd = 0.48 +/- 0.05 nM）相似。LH/CG受体富含亮氨酸重复序列1-8被用于替代促卵泡激素（FSH）密切相关受体中的同源序列。表达此类嵌合LH/CG-FSH受体的细胞结合hCG，并且在受到hCG刺激而非重组人FSH（rhFSH）刺激时显示出升高的环磷酸腺苷水平。同样，一种富含亮氨酸重复序列1-11源自FSH受体的嵌合LH/CG受体被rhFSH激活，但不被hCG激活。对于这种嵌合体，在2 pM至10 nM的范围内未观察到残留的[125I] hCG结合。我们的结果表明，促性腺激素受体的特异性由氨基末端富含亮氨酸的受体重复序列形成的高亲和力激素结合位点决定。
