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

被引：29

作者：

Claeysen, S

Govaerts, C

Lefort, A

Van Sande, J

Costagliola, S

Pardo, L

Vassart, G

机构：

[1] Free Univ Brussels, IRIBHN, B-1070 Brussels, Belgium

[2] Univ Autonoma Barcelona, Fac Med, Unit Bioestadist, Lab Med Computac, Bellaterra 08193, Spain

来源：

FEBS LETTERS | 2002年 / 517卷 / 1-3期

关键词：

G protein-coupled receptor; thyroid-stimulating hormone receptor; constitutive activity; natural mutation; activation mechanism;

D O I：

10.1016/S0014-5793(02)02620-0

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.

引用

页码：195 / 200

页数：6

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