Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore, Karnataka, India.
FEBS Lett. 2012 Mar 23;586(6):810-7. doi: 10.1016/j.febslet.2012.01.052. Epub 2012 Feb 2.
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.
我们报告了两种抗体，scFv 13B1 和 MAb PD1.37，分别针对 LHR 和 TSHR 的铰链区，它们具有相似的表位，但对受体功能有不同的影响。虽然它们都不影响激素结合，对激素反应的影响也很小，但 scFv 13B1 以剂量依赖的方式刺激 LHR，而 MAb PD1.37 作为 TSHR 的反向激动剂。此外，PD1.37 可以降低铰链区 CAMs 的基础活性，但对 ECLs 中存在的 CAMs 有不同的影响，而 13B1 对 LHR 中的任何 CAMs 都没有反应。通过截短突变体和肽噬菌体展示，我们比较了铰链区半胱氨酸盒 2/3 以及外显环在这两种同源受体激活中的差异作用。
