Muscarinic receptor structures compared

The muscarinic acetylcholine receptors (mAChRs) constitute a family of G-protein-coupled receptors. These membrane proteins are targets for treatment of a broad range of conditions, including Alzheimer's disease, schizophrenia and chronic obstructive pulmonary disease. The five mAChR subtypes (M1–M5) share a high degree of sequence homology, but show marked differences in G-protein-coupling preference and physiological function. This pair of papers from Brian Kobilka's group presents the structures of two of the five subtypes. Haga et al . report the X-ray crystal structure of the M2 receptor, which is essential for the physiological control of cardiovascular function; Kruse et al . determine the structure of the M3 receptor, active in the bronchial airways and elsewhere. Comparison of the two structures reveals key differences that could potentially be exploited to develop subtype-selective drugs.