Insights into differential modulation of receptor function by hinge region using novel agonistic lutropin receptor and inverse agonistic thyrotropin receptor antibodies

Insights into differential modulation of receptor function by hinge region using novel agonistic lutropin receptor and inverse agonistic thyrotropin receptor antibodies
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使用新型激动性促甲状腺素受体和反激动性促甲状腺激素受体抗体深入了解铰链区受体功能的差异调节

DOI:
10.1016/j.febslet.2012.01.052
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发表时间:
2012
期刊:
影响因子:
3.5
通讯作者:
R. Dighe
R. Dighe
中科院分区:
生物学3区
文献类型:
--
作者:
R. Majumdar;R. Railkar;R. Dighe

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We report two antibodies, scFv 13B1 and MAb PD1.37, against the hinge regions of LHR and TSHR, respectively, which have similar epitopes but different effects on receptor function. While neither of them affected hormone binding, with marginal effects on hormone response, scFv 13B1 stimulated LHR in a dose-dependent manner, whereas MAb PD1.37 acted as an inverse agonist of TSHR. Moreover, PD1.37 could decrease the basal activity of hinge region CAMs, but had varied effects on those present in ECLs, whereas 13B1 was refractory to any CAMs in LHR. Using truncation mutants and peptide phage display, we compared the differential roles of the hinge region cysteine box-2/3 as well as the exoloops in the activation of these two homologus receptors.
细胞外结构域抑制人类 TSH 受体跨膜结构域的组成活性:对激素-受体相互作用和拮抗剂设计的影响。
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