GPCR structures aided drug design

Abstract

G protein-coupled receptors, or GPCRs, are the largest family of human proteins, with over 800 members. They reside within cell membranes, receiving molecular signals from outside the cell and translating them into signals that influence cellular pathways inside the cell. In 2000 researchers obtained the first GPCR crystal structure, and a decade ago they got the second one. The analysis of GPCR structures began a new chapter in drug discovery, enabling researchers to better design GPCR-targeted medicines. When a signaling molecule, such as a hormone, binds to the part of a GPCR that protrudes from the cell, the receptor undergoes a conformational change that activates a G protein (guanine nucleotide-binding protein) bound to the part of the GPCR that's inside the cell. The activated G protein then modulates the activity of other proteins and signaling pathways. GPCRs are targets of many drugs designed to influence those pathways, including treatments for