par Claeysen, Sylvie ;Govaerts, Cédric ;Lefort, Anne ;Van Sande, Jacqueline ;Costagliola, Sabine ;Pardo, Leonardo;Vassart, Gilbert
Référence FEBS letters, 517, 1-3, page (195-200)
Publication Publié, 2002-04
Référence FEBS letters, 517, 1-3, page (195-200)
Publication Publié, 2002-04
Article révisé par les pairs
Résumé : | 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. |