Molecular Mechanism of Action of Pharmacoperone Rescue of Misrouted GPCR Mutants: The GnRH Receptor

• Published in: Molecular endocrinology (Baltimore, Md.) Vol. 23; no. 2; pp. 157 - 168
• Main Authors: Janovick, Jo Ann, Patny, Akshay, Mosley, Ralph, Goulet, Mark T, Altman, Michael D, Rush, Thomas S, Cornea, Anda, Conn, P. Michael
• Format: Journal Article
• Language: English
• Published: United States Endocrine Society 01.02.2009; Oxford University Press; The Endocrine Society
• Subjects: Animals; Cattle; Cell Membrane - metabolism; Computer Simulation; Humans; Ligands; Models, Molecular; Molecular Chaperones - metabolism; Molecular Structure; Mutagenesis, Site-Directed; Mutation; Protein Binding; Protein Conformation; Protein Transport - physiology; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - metabolism; Receptors, LHRH - genetics; Receptors, LHRH - metabolism

The human GnRH receptor (hGnRHR), a G protein-coupled receptor, is a useful model for studying pharmacological chaperones (pharmacoperones), drugs that rescue misfolded and misrouted protein mutants and restore them to function. This technique forms the basis of a therapeutic approach of rescuing mu...