Cell signalling caught in the act

http://www.nature.com/news/2011/110719/full/475273a.html

The structure of this complex could finally reveal how one of biology's most important signalling mechanisms, G-protein-coupled receptors (GPCRs), do their job. This structure, published online in Nature1 by a team led by Kobilka at Stanford University in California and Roger Sunahara at the University of Michigan in Ann Arbor, now reveals the complete three-dimensional atomic structure of an activated GPCR — the β2 adrenergic receptor (β2AR) — in a complex with its G protein.

GPCRs sit in the membranes of cells throughout the body, where they detect signals from the outside world — such as light, odours and flavours — and signals from within the body, such as hormones and neurotransmitters. These signals are transmitted to the inside of the cell where they activate intracellular G proteins, which then trigger a variety of biochemical pathways.

The β2AR is activated by the hormones adrenaline and noradrenaline, and kicks off the body's fight-or-flight response by speeding up the heart and opening airways. It is a key target for anti-asthma drugs. Kobilka's X-ray crystallographic snapshot of β2AR associated with its G protein reveals some surprises, and could help in the design of more effective medicines — GPCRs are targeted by between one-third and one-half of all drugs on the market, including most of the best-sellers.