Abstract
Class A G protein-coupled receptors have evolved to recognize ligands ranging from small-molecule odorants to proteins. Although they are among the most diverse membrane receptors in eukaryotic organisms, they possess a highly conserved core within their seven-transmembrane helix framework. The conservation of the transmembrane core has led to the idea of a common mechanism by which ligand binding is coupled to the outward rotation of helix H6, the hallmark of an active receptor. Nevertheless, there is still no consensus on the mechanism of coupling or on the roles of specific residues within the core. Recent insights from crystallography and NMR spectroscopy provide a way to decompose the core into its essential structural and functional elements that shed new light on this important region.