The luteinizing hormone receptor (LHR) is a member of the superfamily of G protein-coupled receptors and, in humans, binds two closely related ligands, members of the heterodimer glycoprotein hormone family. This receptor is an essential component of the reproductive axis in males and females and is particularly prone to spontaneous pathogenic activating and inactivating mutations.3D-model building and computer simulations have been employed to study the mutation-induced activation mechanism of the LHR.The results of molecular simulations on different LHR models converge into the hypothesis that the arginine of E/DRY/W sequence is an important switch of the LHR activation. They also suggest that a structural modification at the interface between the cytosolic extensions of helix 3 and helix 6 is important in the mutation-induced LHR activation and/or G protein recognition. The theoretical models provide insights into the structural features of the LHR sites susceptible to spontaneous activating mutations, constituting also useful tools for "in silico" prediction of the functional behaviour of LHR mutants.

Understanding the mutation-induced activation of the lutropin receptor from computer simulation / Fanelli, Francesca. - STAMPA. - (2002), pp. 29-38. (Intervento presentato al convegno 12th European Workshop on Molecular and Cellular Endocrinology of the Testis tenutosi a DOORWERTH, NETHERLANDS nel APR 06-10, 2002).

Understanding the mutation-induced activation of the lutropin receptor from computer simulation

FANELLI, Francesca
2002

Abstract

The luteinizing hormone receptor (LHR) is a member of the superfamily of G protein-coupled receptors and, in humans, binds two closely related ligands, members of the heterodimer glycoprotein hormone family. This receptor is an essential component of the reproductive axis in males and females and is particularly prone to spontaneous pathogenic activating and inactivating mutations.3D-model building and computer simulations have been employed to study the mutation-induced activation mechanism of the LHR.The results of molecular simulations on different LHR models converge into the hypothesis that the arginine of E/DRY/W sequence is an important switch of the LHR activation. They also suggest that a structural modification at the interface between the cytosolic extensions of helix 3 and helix 6 is important in the mutation-induced LHR activation and/or G protein recognition. The theoretical models provide insights into the structural features of the LHR sites susceptible to spontaneous activating mutations, constituting also useful tools for "in silico" prediction of the functional behaviour of LHR mutants.
2002
12th European Workshop on Molecular and Cellular Endocrinology of the Testis
DOORWERTH, NETHERLANDS
APR 06-10, 2002
29
38
Fanelli, Francesca
Understanding the mutation-induced activation of the lutropin receptor from computer simulation / Fanelli, Francesca. - STAMPA. - (2002), pp. 29-38. (Intervento presentato al convegno 12th European Workshop on Molecular and Cellular Endocrinology of the Testis tenutosi a DOORWERTH, NETHERLANDS nel APR 06-10, 2002).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/586784
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