Molecular basis for high-affinity agonist binding in GPCRs

A GPCR seen in the active state G protein–coupled receptors (GPCRs) are exceptionally good targets for drug development. Warneet al. describe four crystal structures of complexes of a GPCR—the β1-adrenergic receptor—in its active state. They used nanobodies (recombinant variable domains of heavy-chain antibodies) and engineered G protein to stabilize the β1-adrenergic receptor bound to a full agonist, two partial agonists, and a weak partial agonist. Comparison of these structures to the inactive state elucidates how agonist binding is altered in the active conformation.Science , this issue p.775