ArticleProceedings of the National Academy of Sciences of the United States of America2004
Identification of core amino acids stabilizing rhodopsin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 165 citations in OpenAlex.
- A Minimalist Model for Navigating Conformational Landscape Uncovers the Activation Mechanism of βACS physical chemistry Au · 2026Article
- Molecular basis of antagonism of the dimeric human arginine vasopressin receptor 1A.Nature communications · 2026Article
- G-protein-coupled receptor diversity and evolution in the closest living relatives of metazoa.eLife · 2025Article
- Mechanisms of Rhodopsin-Related Inherited Retinal Degeneration and Pharmacological Treatment Strategies.Cells · 2025Review
- Dark nanodiscs for evaluating membrane protein thermostability by differential scanning fluorimetry.Biophysical journal · 2024Article
- Dynamics of the Second Extracellular Loop Control Transducer Coupling of Peptide-Activated GPCRs.International journal of molecular sciences · 2023Article
- Activation and Speciation Mechanisms in Class A GPCRs.Journal of molecular biology · 2022Article
- Structural insight into the activation mechanism of MrgD with heterotrimeric Gi-protein revealed by cryo-EM.Communications biology · 2022Article
- Magic angle spinning NMR of G protein-coupled receptors.Progress in nuclear magnetic resonance spectroscopy · 2022Review
- New insights into the molecular mechanism of rhodopsin retinitis pigmentosa from the biochemical and functional characterization of G90V, Y102H and I307N mutations.Cellular and molecular life sciences : CMLS · 2022Article
- Rhodopsin as a Molecular Target to Mitigate Retinitis Pigmentosa.Advances in experimental medicine and biology · 2022Review
- Structure network-based landscape of rhodopsin misfolding by mutations and algorithmic prediction of small chaperone action.Computational and structural biotechnology journal · 2021Article
- Folding and Misfolding of Human Membrane Proteins in Health and Disease: From Single Molecules to Cellular Proteostasis.Chemical reviews · 2019Article
- Comparison of the molecular properties of retinitis pigmentosa P23H and N15S amino acid replacements in rhodopsin.PloS one · 2019Article
- A Small Chaperone Improves Folding and Routing of Rhodopsin Mutants Linked to Inherited Blindness.iScience · 2018Article
- Chemistry and Enzymology of Disulfide Cross-Linking in Proteins.Chemical reviews · 2018Review
- Soft Vibrational Modes Predict Breaking Events during Force-Induced Protein Unfolding.Biophysical journal · 2018Article
- Flavonoid allosteric modulation of mutated visual rhodopsin associated with retinitis pigmentosa.Scientific reports · 2017Article
- G Protein-Coupled Receptors Contain Two Conserved Packing Clusters.Biophysical journal · 2017Article
- Matching Multiple Rigid Domain Decompositions of Proteins.IEEE transactions on nanobioscience · 2017Article
5 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
Rhodopsin is the only G protein-coupled receptor (GPCR) whose 3D structure is known; therefore, it serves as a prototype for studies of the GPCR family of proteins. Rhodopsin dysfunction has been linked to misfolding, caused by chemical modifications that affect the naturally occurring disulfide bond between C110 and C187. Here, we identify the structural elements that stabilize rhodopsin by computational analysis of the rhodopsin structure and comparison with data from previous in vitro mutational studies. We simulate the thermal unfolding of rhodopsin by breaking the native-state hydrogen bonds sequentially in the order of their relative strength, using the recently developed Floppy Inclusion and Rigid Substructure Topography (FIRST) method [Jacobs, D. J., Rader, A. J., Kuhn, L. A. & Thorpe, M. F. (2001) Proteins 44, 150-165]. Residues most stable under thermal denaturation are part of a core, which is assumed to be important for the formation and stability of folded rhodopsin. This core includes the C110-C187 disulfide bond at the center of residues forming the interface between the transmembrane and the extracellular domains near the retinal binding pocket. Fast mode analysis of rhodopsin using the Gaussian network model also identifies the disulfide bond and the retinal ligand binding pocket to be the most rigid region in rhodopsin. Experiments confirm that 90% of the amino acids predicted by the FIRST method to be part of the core cause misfolding upon mutation. The observed high degree of conservation (78.9%) of this disulfide bond across all GPCR classes suggests that it is critical for the stability and function of GPCRs.
Indexed as
Identifiers
What OpenQuestion holds
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.