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Structural Insights into Sigma1 Function

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Sigma Proteins: Evolution of the Concept of Sigma Receptors

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 244))

Abstract

Sigma1 (also known as this sigma-1 receptor) is an unusual and enigmatic transmembrane protein implicated in a diverse array of biological processes ranging from neurodegenerative disease to cancer. Despite decades of research, the molecular architecture of Sigma1 is only beginning to become clear. Recent work has established that Sigma1 is an oligomer, and crystallographic studies have now offered the first high-resolution views of its molecular structure. For the first time, these results provide a detailed framework to understand mutagenesis data and the molecular pharmacology of Sigma1 ligands. Structural data also raise new questions surrounding the mechanisms of ligand activity and the molecular basis for interactions between Sigma1 and other proteins. As Sigma1 research enters the structural era, the field is poised for new discoveries and reevaluation of old data and old models.

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Authors and Affiliations

  1. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Seeley G. Mudd Building, 250 Longwood Ave., Boston, MA, 02115, USA

    Andrew Kruse

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  1. Andrew Kruse
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Correspondence to Andrew Kruse .

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Editors and Affiliations

  1. Pharmacology & Physiology, Drexel University College of Medicine, Philadelphia, Pennsylvania, USA

    Felix J. Kim

  2. Molecular Pharmacology and Chemistry, Memorial Sloan-Kettering Cancer Center, New York, New York, USA

    Gavril W. Pasternak

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Kruse, A. (2016). Structural Insights into Sigma1 Function. In: Kim, F., Pasternak, G. (eds) Sigma Proteins: Evolution of the Concept of Sigma Receptors. Handbook of Experimental Pharmacology, vol 244. Springer, Cham. https://doi.org/10.1007/164_2016_95

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