σ1 Receptor ligand binding: an open-and-shut case

The σ1 receptor, an endoplasmic reticulum–resident transmembrane protein, modulates many physiological and pathological processes and binds multiple drugs, but is nonetheless poorly understood. In a recent issue, Kruse and colleagues illustrate structural differences between agonist- and antagonist-bound receptor and propose that agonist binding may impair oligomerization, making a major step in understanding σ1 function. They also use a combination of kinetic and molecular dynamic modeling to explain how ligands access the binding pocket.