ArticleProceedings of the National Academy of Sciences of the United States of America2021
Mechanisms underlying drug-mediated regulation of membrane protein function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Probing non-covalent membrane protein-lipid interactions using sheath liquid capillary electrophoresis-native top-down mass spectrometry.The Analyst · 2026Article
- Ultra-slow release of hydrophilic drugs via multilamellar-multivesicular liposomes formed by unsaturated phospholipids.Nature biomedical engineering · 2026Article
- Lipid bilayers determine allostery but not intrinsic affinity of cAMP to pacemaker channels.Nature communications · 2026Article
- The Evolution of Lipids from Solvents to Substrates.Annual review of biophysics · 2026Review
- Targeting the AcrAB-TolC efflux pump by small molecules selectively addressing the outer membrane factor TolC.Frontiers in pharmacology · 2026Article
- Membrane Perturbations and Assay Interferences by Ivermectin Explain Its In Vitro SARS-CoV-2 Antiviral Activities and Lack of Translatability.Journal of medicinal chemistry · 2025Review
- Inhibitory Effect of Amentoflavone on the Virulence of MRSA by Targeting ClpP.Journal of cellular and molecular medicine · 2025Article
- Dimeric Tubulin Modifies Mechanical Properties of Lipid Bilayer, as Probed Using Gramicidin A Channel.International journal of molecular sciences · 2024Article
- Nonspecific membrane bilayer perturbations by ivermectin underlie SARS-CoV-2bioRxiv : the preprint server for biology · 2023Article
- Screening for bilayer-active and likely cytotoxic molecules reveals bilayer-mediated regulation of cell function.The Journal of general physiology · 2023Article
- Getting in on the action: New tools to see SARS-CoV-2 infect a cell.Cell chemical biology · 2023Article
- Changes in Electrical Capacitance of Cell Membrane Reflect Drug Partitioning-Induced Alterations in Lipid Bilayer.Micromachines · 2023Article
- Capsaicin as an amphipathic modulator of NaChannels (Austin, Tex.) · 2022Article
- Asymmetric effects of amphipathic molecules on mechanosensitive channels.Scientific reports · 2022Article
- Regulation of Gramicidin Channel Function Solely by Changes in Lipid Intrinsic Curvature.Frontiers in physiology · 2022Article
- Mechanisms underlying drug-mediated regulation of membrane protein function.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The hydrophobic coupling between membrane proteins and their host lipid bilayer provides a mechanism by which bilayer-modifying drugs may alter protein function. Drug regulation of membrane protein function thus may be mediated by both direct interactions with the protein and drug-induced alterations of bilayer properties, in which the latter will alter the energetics of protein conformational changes. To tease apart these mechanisms, we examine how the prototypical, proton-gated bacterial potassium channel KcsA is regulated by bilayer-modifying drugs using a fluorescence-based approach to quantify changes in both KcsA function and lipid bilayer properties (using gramicidin channels as probes). All tested drugs inhibited KcsA activity, and the changes in the different gating steps varied with bilayer thickness, suggesting a coupling to the bilayer. Examining the correlations between changes in KcsA gating steps and bilayer properties reveals that drug-induced regulation of membrane protein function indeed involves bilayer-mediated mechanisms. Both direct, either specific or nonspecific, binding and bilayer-mediated mechanisms therefore are likely to be important whenever there is overlap between the concentration ranges at which a drug alters membrane protein function and bilayer properties. Because changes in bilayer properties will impact many diverse membrane proteins, they may cause indiscriminate changes in protein function.
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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.