ArticleProceedings of the National Academy of Sciences of the United States of America2018
Ligand channel in pharmacologically stabilized rhodopsin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- New Fluorescent Probes for Visual Proteins. Part III. Probing Auxiliary Gateways and the Stepwise Activation Model of Ligand Transport.Journal of fluorescence · 2026Article
- Structural analysis of rhodopsin states in megabody complexes.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Small-Molecule Ligands of Rhodopsin and Their Therapeutic Potential in Retina Degeneration.International journal of molecular sciences · 2025Review
- Identification of a Non-Retinoid Opsin Ligand Through Pharmacophore-Guided Virtual Screening-A Novel Potential Rhodopsin-Stabilizing Compound.Molecules (Basel, Switzerland) · 2025Article
- Mechanisms of Rhodopsin-Related Inherited Retinal Degeneration and Pharmacological Treatment Strategies.Cells · 2025Review
- Exploring the potential of pheophorbide A, a chlorophyll-derived compound in modulating GLUT for maintaining glucose homeostasis.Frontiers in endocrinology · 2024Article
- Chromenone derivatives as novel pharmacological chaperones for retinitis pigmentosa-linked rod opsin mutants.Human molecular genetics · 2022Article
- Nonretinoid chaperones improve rhodopsin homeostasis in a mouse model of retinitis pigmentosa.JCI insight · 2022Article
- FRET sensors reveal the retinal entry pathway in the G protein-coupled receptor rhodopsin.iScience · 2022Article
- Flavonoids improve the stability and function of P23H rhodopsin slowing down the progression of retinitis pigmentosa in mice.Journal of neuroscience research · 2022Article
- Rhodopsin as a Molecular Target to Mitigate Retinitis Pigmentosa.Advances in experimental medicine and biology · 2022Review
- The GFP thermal shift assay for screening ligand and lipid interactions to solute carrier transporters.Nature protocols · 2021Review
- Structural aspects of rod opsin and their implication in genetic diseases.Pflugers Archiv : European journal of physiology · 2021Review
- Structure network-based landscape of rhodopsin misfolding by mutations and algorithmic prediction of small chaperone action.Computational and structural biotechnology journal · 2021Article
- Assistance for Folding of Disease-Causing Plasma Membrane Proteins.Biomolecules · 2020Review
- Multiscale Molecular Modeling in G Protein-Coupled Receptor (GPCR)-Ligand Studies.Biomolecules · 2020Review
- Strategic Screening and Characterization of the Visual GPCR-mini-G Protein Signaling Complex for Successful Crystallization.Journal of visualized experiments : JoVE · 2020Article
- The Retinoid and Non-Retinoid Ligands of the Rod Visual G Protein-Coupled Receptor.International journal of molecular sciences · 2019Review
- Screening of Chemical Libraries Using a Yeast Model of Retinal Disease.SLAS discovery : advancing life sciences R & D · 2019Article
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the degenerative eye disease retinitis pigmentosa (RP), protein misfolding leads to fatal consequences for cell metabolism and rod and cone cell survival. To stop disease progression, a therapeutic approach focuses on stabilizing inherited protein mutants of the G protein-coupled receptor (GPCR) rhodopsin using pharmacological chaperones (PC) that improve receptor folding and trafficking. In this study, we discovered stabilizing nonretinal small molecules by virtual and thermofluor screening and determined the crystal structure of pharmacologically stabilized opsin at 2.4 Å resolution using one of the stabilizing hits (S-RS1). Chemical modification of S-RS1 and further structural analysis revealed the core binding motif of this class of rhodopsin stabilizers bound at the orthosteric binding site. Furthermore, previously unobserved conformational changes are visible at the intradiscal side of the seven-transmembrane helix bundle. A hallmark of this conformation is an open channel connecting the ligand binding site with the membrane and the intradiscal lumen of rod outer segments. Sufficient in size, the passage permits the exchange of hydrophobic ligands such as retinal. The results broaden our understanding of rhodopsin's conformational flexibility and enable therapeutic drug intervention against rhodopsin-related retinitis pigmentosa.
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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.