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Structural Perspectives on Sigma-1 Receptor Function

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Sigma Receptors: Their Role in Disease and as Therapeutic Targets

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 964))

Abstract

The sigma-1 receptor is an enigmatic ER-resident transmembrane protein linked to a variety of human diseases. Although the receptor was first cloned 20 years ago, the molecular structure of the protein and the mechanistic basis for its interaction with drug-like small molecules have remained unclear until recently. The determination of the first crystal structure of human sigma-1 offered the first detailed views of the sigma-1 architecture, and revealed an unusual overall fold with a single transmembrane helix in each protomer. The structure shows an overall trimeric receptor arrangement, and each protomer binds a single ligand molecule at the center of its carboxy-terminal domain. These results offer detailed molecular views of receptor structure, oligomerization, and ligand recognition, providing a framework for the next era of sigma-1 research.

Authors (Assaf Alon, Hayden Schmidt, Sanduo Zheng) contributed equally and are listed in alphabetical order.

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Author information

Authors and Affiliations

  1. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA

    Assaf Alon, Hayden Schmidt, Sanduo Zheng & Andrew C. Kruse

Authors
  1. Assaf Alon
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  2. Hayden Schmidt
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  3. Sanduo Zheng
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  4. Andrew C. Kruse
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Corresponding author

Correspondence to Andrew C. Kruse .

Editor information

Editors and Affiliations

  1. Departments of Cellular Biology and Anatomy and Ophthalmology and the James and Jean Culver Vision Discovery Institute, Medical College of Georgia at Augusta University, Augusta, Georgia, USA

    Sylvia B. Smith

  2. Cellular Pathobiology Section, Integrative Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, US Department of Health and Human Services, Baltimore, Maryland, USA

    Tsung-Ping Su

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Alon, A., Schmidt, H., Zheng, S., Kruse, A.C. (2017). Structural Perspectives on Sigma-1 Receptor Function. In: Smith, S., Su, TP. (eds) Sigma Receptors: Their Role in Disease and as Therapeutic Targets. Advances in Experimental Medicine and Biology, vol 964. Springer, Cham. https://doi.org/10.1007/978-3-319-50174-1_2

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