ArticleNature communications2024
Insight into binding of endogenous neurosteroid ligands to the sigma-1 receptor.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed.
- MD Simulations of Human Sigma-1 Receptor Trimer Uncover Cholesterol-Dependent Stabilization and Ligand-Specific Dynamics.Journal of chemical information and modeling · 2026Article
- Sigma receptor ligands in selected affective disorders, psychoses, and addictions - a narrative review.Pharmacological reports : PR · 2026Review
- The total mass, copy number, and distribution of hormones in the human bloodstream.PLoS biology · 2026Article
- New pharmacological agents and emerging therapeutic targets for painful diabetic neuropathy.Frontiers in endocrinology · 2026Review
- SigmaR1 is an auxiliary translocon factor with lipid-binding activity that regulates protein and lipid droplet homeostasis.Nature communications · 2025Article
- Prediction of Activity and Selectivity Profiles of Sigma Receptor Ligands Using Machine Learning Approaches.Journal of chemical information and modeling · 2025Article
- Could R-Ketamine and Wolfram Syndrome Inform Understanding of Depression and Suicidality? A Sigma-1 Receptor-Based Perspective.Human psychopharmacology · 2025Review
- Choline-An Essential Nutrient with Health Benefits and a Signaling Molecule.International journal of molecular sciences · 2025Review
- Neurosteroids Progesterone and Dehydroepiandrosterone: Molecular Mechanisms of Action in Neuroprotection and Neuroinflammation.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Recent Advances in the Development of Sigma Receptor (Radio)Ligands and Their Application in Tumors.ACS pharmacology & translational science · 2025Review
- Advancing depression treatment: the role of sigma receptor ligands.Frontiers in neuroscience · 2025Review
- The sigma-1 receptor as a neurohomeostatic decision hub for GABARAP-mediated receptor trafficking and macroautophagy.Frontiers in molecular biosciences · 2025Article
Corrections and comments
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Authors and funding
4 authors.
Funding
Abstract
The sigma-1 receptor (σ1R) is a non-opioid membrane receptor, which responds to a diverse array of synthetic ligands to exert various pharmacological effects. Meanwhile, candidates for endogenous ligands of σ1R have also been identified. However, how endogenous ligands bind to σ1R remains unknown. Here, we present crystal structures of σ1R from Xenopus laevis (xlσ1R) bound to two endogenous neurosteroid ligands, progesterone (a putative antagonist) and dehydroepiandrosterone sulfate (DHEAS) (a putative agonist), at 2.15-3.09 Å resolutions. Both neurosteroids bind to a similar location in xlσ1R mainly through hydrophobic interactions, but surprisingly, with opposite binding orientations. DHEAS also forms hydrogen bonds with xlσ1R, whereas progesterone interacts indirectly with the receptor through water molecules near the binding site. Binding analyses are consistent with the xlσ1R-neurosteroid complex structures. Furthermore, molecular dynamics simulations and structural data reveal a potential water entry pathway. Our results provide insight into binding of two endogenous neurosteroid ligands to σ1R.
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Registered trials
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