Inactivating mutations of G protein-coupled receptors and diseases: structure-function insights and therapeutic implications.

摘要: Since the discovery of first rhodopsin mutation that causes retinitis pigmentosa in 1990, significant progresses have been made elucidating pathophysiology diseases caused by inactivating mutations G protein-coupled receptors (GPCRs). This review aims to compile compelling evidence accumulated during past 15 years demonstrating etiologies more than a dozen GPCR mutations. A generalized classification scheme, based on life cycle GPCRs, is proposed. Insights gained through detailed studies these naturally occurring into structure-function relationship are reviewed. Therapeutic approaches directed against different classes mutants being developed. intracellular retention emerges as most common defect, recent aimed at correcting this defect membrane permeable pharmacological chaperones highlighted.