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Dissecting the structural and functional features of the Luteinizing hormone receptor using receptor specific single chain fragment variables

Dhar, Neha and Mohan, Abhilash and Thakur, Chandrani and Chandra, Nagasuma R and Dighe, Rajan R (2016) Dissecting the structural and functional features of the Luteinizing hormone receptor using receptor specific single chain fragment variables. In: MOLECULAR AND CELLULAR ENDOCRINOLOGY, 427 (C). pp. 1-12.

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Official URL: http://dx.doi.org/10.1016/j.mce.2016.02.022

Abstract

The Luteinizing hormone receptor (LHR) has a large extracellular domain (amino acid residues, a.a.1 -355) and a transmembrane domain (TMD; a.a. 356-699), essential for hormone binding and signaling, respectively. The LHR hinge region (a.a. 256-355) connects the two domains and acts as an activating switch for the receptor by an unknown mechanism. LHR hinge-specific Single chain fragment variables (ScFv) stimulated cAMP production by the stable and transiently transfected cell lines expressing LHR in a hormone-independent manner and the C-terminal region of LHR hinge (a.a. 313-349) was identified as the probable epitope for one agonistic ScFv. This epitope attained a helical conformation upon agonistic ScFv binding and the activity of the ScFv was dependent on Y331 sulfation. ScFv was also able to activate TMD mutants, D578Y and A593P, reemphasizing the role of TM helix VI in LHR activation. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

Item Type: Journal Article
Additional Information: Copy right for this article belongs to the ELSEVIER IRELAND LTD, ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND
Keywords: Glycoprotein hormones; Luteinizing hormone receptor; Hinge region; Phage display; Agonistic antibodies; Conformational change
Department/Centre: Division of Biological Sciences > Biochemistry
Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Depositing User: Id for Latest eprints
Date Deposited: 10 Jun 2016 06:27
Last Modified: 10 Jun 2016 06:27
URI: http://eprints.iisc.ac.in/id/eprint/53872

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