ArticleNature2016
Crystal structure of the human σ1 receptor.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 257 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
257 citing papers in PubMed, 456 citations in OpenAlex.
- The landscape of cocaine cytotoxicity and the role of sigma-1 receptor modulation and adulterant synergism.Archives of toxicology · 2026Review
- Machine Learning-Driven Discovery of Indole/Oxoindole-Piperazine Scaffolds as Dual MAO-B/Sig-1R Ligands for Neurodegenerative Disorders.Journal of chemical information and modeling · 2026Article
- Sigma1 Receptor Activation Confers Durable Neuroprotection Following Neonatal Ischemic Retinal Injury.Research square · 2026Article
- MD Simulations of Human Sigma-1 Receptor Trimer Uncover Cholesterol-Dependent Stabilization and Ligand-Specific Dynamics.Journal of chemical information and modeling · 2026Article
- Article
- Targeting endoplasmic reticulum stress and protein misfolding in schizophrenia: the emerging promise of sigma-1 receptor agonists.Psychopharmacology · 2026Review
- Sigma 1 Receptor Activation Coordinates Metabolic Stress Responses to Protect Retinal Vasculature in Ischemic Retinopathy.Investigative ophthalmology & visual science · 2026Article
- Targeting Neuroinflammation in Depression: The Integrative Role of Sigma-1 Receptor Modulation.Journal of neurochemistry · 2026Review
- The Role of Sigmar1 in Autophagy Regulation and Disease Therapy.International journal of molecular sciences · 2026Review
- Sigma-1 receptor positive allosteric modulator promotes neuronal survival and improves cognitive deficits in AD mice via sigma-1 receptor/ERK pathway.Acta pharmacologica Sinica · 2026Article
- Targeting Sigma-1 and Sigma-2 Receptors in Neuropathic Pain: Pharmacology, Ligand Development, and Translational Progress.Brain sciences · 2026Review
- Modulation of Tau Protein Neurotoxic Hallmarks by Novel σChemMedChem · 2026Article
- Bis-hydrophobic 5-(1,2-dithiolan-3-yl)pentanamide budding leads targeting brain sigma-1 receptors.PloS one · 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
- Sigma-1 Receptor Ligands for CNS Cancer Treatment.CNS drugs · 2025Review
- A Full-Spectrum Evaluation of Sigma-1 Receptor (S1R) Positron Emission Tomography (PET) Radioligands from Binding Affinity to Clinical Imaging.Molecules (Basel, Switzerland) · 2025Review
- Integrated control of cancer stemness by σOncogene · 2025Article
- Discovery and proof-of-concept study of a novel highly selective sigma-1 receptor agonist for antipsychotic drug development.Acta pharmaceutica Sinica. B · 2025Article
- Article
197 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The human σ1 receptor is an enigmatic endoplasmic-reticulum-resident transmembrane protein implicated in a variety of disorders including depression, drug addiction, and neuropathic pain. Recently, an additional connection to amyotrophic lateral sclerosis has emerged from studies of human genetics and mouse models. Unlike many transmembrane receptors that belong to large, extensively studied families such as G-protein-coupled receptors or ligand-gated ion channels, the σ1 receptor is an evolutionary isolate with no discernible similarity to any other human protein. Despite its increasingly clear importance in human physiology and disease, the molecular architecture of the σ1 receptor and its regulation by drug-like compounds remain poorly defined. Here we report crystal structures of the human σ1 receptor in complex with two chemically divergent ligands, PD144418 and 4-IBP. The structures reveal a trimeric architecture with a single transmembrane domain in each protomer. The carboxy-terminal domain of the receptor shows an extensive flat, hydrophobic membrane-proximal surface, suggesting an intimate association with the cytosolic surface of the endoplasmic reticulum membrane in cells. This domain includes a cupin-like β-barrel with the ligand-binding site buried at its centre. This large, hydrophobic ligand-binding cavity shows remarkable plasticity in ligand recognition, binding the two ligands in similar positions despite dissimilar chemical structures. Taken together, these results reveal the overall architecture, oligomerization state, and molecular basis for ligand recognition by this important but poorly understood protein.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.