Published in

American Association for the Advancement of Science, Science, 6500(369), p. 161-167, 2020

DOI: 10.1126/science.aax2517

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Structure and selectivity engineering of the M <sub>1</sub> muscarinic receptor toxin complex

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

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