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

doi:https://doi.org/10.1016/S0014-5793(02)02620-0

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

Research output: Contribution to journal › Article › Research › peer-review

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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 language	English
Pages (from-to)	195-200
Journal	FEBS Letters
Volume	517
DOIs	https://doi.org/10.1016/S0014-5793(02)02620-0
Publication status	Published - 24 Apr 2002

Keywords

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

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https://doi.org/10.1016/S0014-5793(02)02620-0

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

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. {\textcopyright} 2002 Federation of European Biochemical Societies. All rights reserved.",

keywords = "Activation mechanism, Constitutive activity, G protein-coupled receptor, Natural mutation, Thyroid-stimulating hormone receptor",

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T1 - A conserved Asn in TM7 of the thyrotropin receptor is a common requirement for activation by both mutations and its natural agonist

AU - Claeysen, Sylvie

AU - Govaerts, Cédric

AU - Lefort, Anne

AU - Van Sande, Jacqueline

AU - Costagliola, Sabine

AU - Pardo, Leonardo

AU - Vassart, Gilbert

PY - 2002/4/24

Y1 - 2002/4/24

N2 - 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.

AB - 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.

KW - Activation mechanism

KW - Constitutive activity

KW - G protein-coupled receptor

KW - Natural mutation

KW - Thyroid-stimulating hormone receptor

U2 - https://doi.org/10.1016/S0014-5793(02)02620-0

DO - https://doi.org/10.1016/S0014-5793(02)02620-0

M3 - Article

VL - 517

SP - 195

EP - 200

ER -

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

Abstract

Keywords

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