In this issue of Structure, Banerjee et al.1 use single-molecule FRET to explore how various detergents and cholesterol influence the conformational dynamics of the extracellular domain of the metabotropic glutamate receptor 2 (mGluR2). They show that the local membrane environment modulates the receptor's active-inactive state equilibrium and identifies specific cholesterol-binding sites, offering insights into potential drug-targeting strategies for mGluR2.
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