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Characterization of the Human Sigma-1 Receptor Chaperone Domain Structure and Binding Immunoglobulin Protein (BiP) Interactions

Ortega-Roldan, Jose L., Ossa, F., Schnell, J. R. (2013) Characterization of the Human Sigma-1 Receptor Chaperone Domain Structure and Binding Immunoglobulin Protein (BiP) Interactions. Journal of Biological Chemistry, 288 (29). pp. 21448-21457. ISSN 0021-9258. (doi:10.1074/jbc.M113.450379) (Access to this publication is currently restricted. You may be able to access a copy if URLs are provided)

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Abstract

The sigma-1 receptor (S1R) is a ligand-regulated membrane protein chaperone involved in the ER stress response. S1R activity is implicated in diseases of the central nervous system including amnesia, schizophrenia, depression, Alzheimer disease, and addiction. S1R has been shown previously to regulate the Hsp70 binding immunoglobulin protein (BiP) and the inositol triphosphate receptor calcium channel through a C-terminal domain. We have developed methods for bacterial expression and reconstitution of the chaperone domain of human S1R into detergent micelles that enable its study by solution NMR spectroscopy. The chaperone domain is found to contain a helix at the N terminus followed by a largely dynamic region and a structured, helical C-terminal region that encompasses a membrane associated domain containing four helices. The helical region at residues ?198–206 is strongly amphipathic and proposed to anchor the chaperone domain to micelles and membranes. Three of the helices in the C-terminal region closely correspond to previously identified cholesterol and drug recognition sites. In addition, it is shown that the chaperone domain interacts with full-length BiP or the isolated nucleotide binding domain of BiP, but not the substrate binding domain, suggesting that the nucleotide binding domain is sufficient for S1R interactions.

Item Type: Article
DOI/Identification number: 10.1074/jbc.M113.450379
Uncontrolled keywords: Endoplasmic Reticulum Stress; Membrane Proteins; NMR; Signaling; Structural Biology; BiP; Sigma-1 Receptor
Subjects: Q Science > QD Chemistry > QD431 Organic Chemistry- Biochemistry- Proteins, peptides, amino acids
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Jose Ortega-Roldan
Date Deposited: 13 Nov 2016 22:47 UTC
Last Modified: 29 May 2019 18:11 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/58602 (The current URI for this page, for reference purposes)
Ortega-Roldan, Jose L.: https://orcid.org/0000-0002-6316-4390
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