With roughly 1,000 different members, G-protein-coupled receptors (GPCRs) are the largest family of proteins coded by the human genome. Involved in sensing a panoply of physiological and environmental signals, including hormones, neurotransmitters, odorants, tastes and light, GPCRs are the targets of a pharmacopeia of drugs, from beta blockers to antihistamines. Until recently, however, high-resolution crystal structures were known for only the light receptor rhodopsin.
In 2007, Brian Kobilka, a biochemist at Stanford University, and Raymond Stevens, a chemist at Scripps Research Institute, cracked the structure of β2-adrenergic receptor (β2AR), a receptor of adrenaline involved in cardiovascular and pulmonary function. After slogging away at the membrane molecule for close to two decades, Kobilka and Stevens had "a parallel and complementary series of technological breakthroughs," recalls Stevens.
Kobilka and colleagues stabilized β2AR by tacking on an antibody fragment. In parallel, he also replaced one of the receptor's flexible intracellular loops with a ...
