A Review of the Human Sigma-1 Receptor Structure.
The Sigma-1 Receptor (S1R) is a small, ligand-regulated integral membrane protein involved in cell homeostasis and the cellular stress response. The receptor has a multitude of protein and small molecule interaction partners with therapeutic potential. Newly reported structures of the human S1R in ligand-bound states provides essential insights into small molecule binding in the context of the overall protein structure. The structure also raises many interesting questions and provides an excellent starting point for understanding the molecular tricks employed by this small membrane receptor to modulate a large number of signaling events. Here, we review insights from the structures of ligand-bound S1R in the context of previous biochemical studies and propose, from a structural viewpoint, a set of important future directions.
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK.
Felipe
F
Ossa
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU, UK. jason.schnell@bioch.ox.ac.uk.
Jason R
JR
Schnell
School of Biosciences, University of Kent, Stacey Building, Room 215B, Canterbury, CT2 7NJ, UK.
José Luis
JL
Ortega-Roldan
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008024:Ligands; D017480:Receptors, sigma / Q000737:chemistry* / Q000378:metabolism*; D016415:Sequence Alignment; D054852:Small Molecule Libraries / Q000737:chemistry / Q000378:metabolism; D000097605:Sigma-1 Receptor
D008024:Ligands; D017480:Receptors, sigma; D054852:Small Molecule Libraries; D000097605:Sigma-1 Receptor
Ligand binding; Membrane protein; Protein oligomerization; Protein structure; Sigma-1 receptor