Structure and selectivity engineering of the M 1 muscarinic receptor toxin complex

Engineering a toxin Developing drugs that target a specific subtype in a G protein–coupled receptor (GPCR) family is a major challenge. Maeda et al. examined the basis of specificity of a snake venom toxin binding to muscarinic acetylcholine receptors (MAChRs), which mediate many functions of the central and parasympathetic nervous systems. They determined a structure that shows why the mamba venom toxin MT7 is specific for one receptor, M 1 AChR, and also explains how it inhibits downstream signaling. Based on this structure, they engineered MT7 to be selective for another receptor, M 2 AChR, instead of M 1 ChR. The toxin may present a promising scaffold for developing specific GPCR modulators. Science , this issue p. 161