ArticleNature chemistry2025
Defining proteoform-specific interactions for drug targeting in a native cell signalling environment.
Article in Nature chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The trial behind it
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Who cites it
20 citing papers in PubMed.
- Targeted proteoform degradation for precision drug design, delivery, and therapy.Drug delivery · 2026Review
- Large-scale single-molecule analysis of tau proteoforms.Nature methods · 2026Article
- Long-Chain S-Acylation Is a Key Modulator During the Macrophage Inflammatory Response.Molecular & cellular proteomics : MCP · 2026Article
- Isotope Decluttering Reduces Spectral Complexity while Maintaining Protein Structure.Analytical chemistry · 2026Article
- Native-Like Protein Structures in Vacuo: Steric Cooperativity as a Kinetic Barrier to Denaturation.JACS Au · 2026Article
- Small subunit isoform diversity underlies structural heterogeneity in native plant Rubisco.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- On the Utility of Infrared Photoactivation for Native Top-Down and Complex-Down Orbitrap Mass Spectrometry of Soluble Proteoform Complexes.Journal of the American Society for Mass Spectrometry · 2026Article
- Quantitative Mapping of NHS Ester-Protein Reactivity Using Native Top-Down Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2026Article
- Implementation of Infrared-Activated Negative Electron Transfer Dissociation (IR-NETD) Using Xenon on a Quadrupole-Orbitrap-Quadrupole Linear Ion Trap Mass Spectrometer.Journal of the American Society for Mass Spectrometry · 2026Article
- Uncovering hidden protein modifications with native top-down mass spectrometry.Nature methods · 2025Article
- Improved Mass Analysis of Proteins and Protein Complexes Present in Common Biological Buffers and Physiological Concentrations of NaCl Using Solution Additives Delivered by Theta Emitters.Analytical chemistry · 2025Article
- Structural Heterogeneity of Proteoform-Ligand Complexes in Adenosine Monophosphate-Activated Protein Kinase Uncovered by Integrated Top-Down Mass Spectrometry.Journal of the American Chemical Society · 2025Article
- Native Top-Down Proteomics of Endogenous Protein Complexes Enabled by Online Two-Dimensional Liquid Chromatography.Analytical chemistry · 2025Article
- Native Top-Down Analysis of Membrane Protein Complexes Directly From In Vitro and Native Membranes.Molecular & cellular proteomics : MCP · 2025Article
- Review
- Normalized and Directional Interplay Scoring for the Interrogation of Proteoform Data.Journal of proteome research · 2025Article
- Traversing the drug discovery landscape using native mass spectrometry.Current opinion in structural biology · 2025Review
- Defining proteoform-specific interactions for drug targeting in a native cell signalling environment.Nature chemistry · 2025Article
- Thermal Remodeling of Human HDL Particles Reveals Diverse Subspecies.Journal of the American Society for Mass Spectrometry · 2024Article
- First 20 Years of Orbitrap Mass Spectrometry as the Mainstream Analytical Technique.Mass spectrometry reviewsReview
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Understanding the dynamics of membrane protein-ligand interactions within a native lipid bilayer is a major goal for drug discovery. Typically, cell-based assays are used, however, they are often blind to the effects of protein modifications. In this study, using the archetypal G protein-coupled receptor rhodopsin, we found that the receptor and its effectors can be released directly from retina rod disc membranes using infrared irradiation in a mass spectrometer. Subsequent isolation and dissociation by infrared multiphoton dissociation enabled the sequencing of individual retina proteoforms. Specifically, we categorized distinct proteoforms of rhodopsin, localized labile palmitoylations, discovered a Gβγ proteoform that abolishes membrane association and defined lipid modifications on G proteins that influence their assembly. Given reports of undesirable side-effects involving vision, we characterized the off-target drug binding of two phosphodiesterase 5 inhibitors, vardenafil and sildenafil, to the retina rod phosphodiesterase 6 (PDE6). The results demonstrate differential off-target reactivity with PDE6 and an interaction preference for lipidated proteoforms of G proteins. In summary, this study highlights the opportunities for probing proteoform-ligand interactions within natural membrane environments.
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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.