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

Majumdar, Ritankar and Railkar, Reema and Dighe, Rajan R (2012) Insights into differential modulation of receptor function by hinge region using novel agonistic lutropin receptor and inverse agonistic thyrotropin receptor antibodies. In: FEBS Letters, 586 (6). pp. 810-817.

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Official URL: http://dx.doi.org/10.1016/j.febslet.2012.01.052

Abstract

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.

Item Type: Journal Article
Additional Information: Copyright of this article belongs to Elsevier Science B.V.
Keywords: GPCR;Agonist;Inverse agonist;Receptor activation; Conformational change;Glycoprotein hormone and receptor
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics (formed by the merger of DBGL and CRBME)
Date Deposited: 01 May 2012 10:51
Last Modified: 01 May 2012 10:51
URI: http://eprints.iisc.ernet.in/id/eprint/44344

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