A conserved Asn in TM7 of the thyrotropin receptor is a common requirement for activation by both mutations and its natural agonist

Sylvie Claeysen, Cédric Govaerts, Anne Lefort, Jacqueline Van Sande, Sabine Costagliola, Leonardo Pardo, Gilbert Vassart

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33 Citations (Scopus)

Abstract

The wide spectrum of naturally occurring mutations able to activate the thyrotropin (TSH) receptor provides a useful tool to approach the structure of the active state(s) of the glycoprotein hormone receptors. Here we show that the side-chain of the highly conserved N7.49 (Asn 674) in TM7 is mandatory for activation of the TSH receptor, not only by TSH, but also by a panel of eight natural and two artificial activating mutations. Basal activity levels of the mutants were significantly decreased by suppression of the side-chain of N7.49 (N7.49A double mutants). In addition, comparative effects of the N7.49A substitution on the ten mutants demonstrate that basal activity and agonist- or mutation-stimulated activity might involve different structural changes. © 2002 Federation of European Biochemical Societies. All rights reserved.
Original languageEnglish
Pages (from-to)195-200
JournalFEBS Letters
Volume517
DOIs
Publication statusPublished - 24 Apr 2002

Keywords

  • Activation mechanism
  • Constitutive activity
  • G protein-coupled receptor
  • Natural mutation
  • Thyroid-stimulating hormone receptor

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