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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.

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Fig. 1: Schematic of σ1 receptor binding.


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Supported by grants from the National Institute on Drug Abuse (DA07242 and DA06241), the Mayday Fund, and the McManus Charitable Trust to G.W.P.; a grant from the National Cancer Institute (CA08748) to SKI, MSKCC; and an American Cancer Society institutional research grant through the Sidney Kimmel Cancer Center at Thomas Jefferson University, a Drexel University Clinical and Translational Research Institute grant, and a Sidney Kimmel Cancer Center Consortium Pilot Study Award to F.J.K.

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Correspondence to Gavril W. Pasternak.

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F.J.K. is a cofounder of Context Therapeutics.

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Kim, F.J., Pasternak, G.W. σ1 Receptor ligand binding: an open-and-shut case. Nat Struct Mol Biol 25, 992–993 (2018).

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