Journal
FEBS LETTERS
Volume 586, Issue 6, Pages 810-817Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2012.01.052
Keywords
GPCR; Agonist; Inverse agonist; Receptor activation; Conformational change; Glycoprotein hormone and receptor
Funding
- Department of Biotechnology, New Delhi, India
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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. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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