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σ1 RECEPTOR

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

Nature Structural & Molecular Biology volume 25, pages 992–993 (2018)Cite this article

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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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Acknowledgements

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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Authors and Affiliations

  1. Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA

    Felix J. Kim

  2. Sidney Kimmel Cancer Center at Thomas Jefferson University, Philadelphia, PA, USA

    Felix J. Kim

  3. Department of Neurology and Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Gavril W. Pasternak

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  1. Felix J. Kim
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  2. Gavril W. Pasternak
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Correspondence to Gavril W. Pasternak.

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Competing interests

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). https://doi.org/10.1038/s41594-018-0146-1

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