ArticleProceedings of the National Academy of Sciences of the United States of America2003
Use of thiol-disulfide equilibria to measure the energetics of assembly of transmembrane helices in phospholipid bilayers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 146 citations in OpenAlex.
- Adamantane-based inhibitors of the influenza A M2 proton channel: structure-based design, biological evaluation, and synthetic approaches.RSC medicinal chemistry · 2026Review
- High-throughput discovery of transmembrane helix dimers from human single-pass membrane proteins with TOXGREEN sort-seq.PNAS nexus · 2025Article
- Molecular biophysics and inhibition mechanism of influenza virus A M2 viroporin by adamantane-based drugs - Challenges in designing antiviral agents.Journal of structural biology: X · 2025Article
- De novo-designed transmembrane proteins bind and regulate a cytokine receptor.Nature chemical biology · 2024Article
- Cholesterol-modified sphingomyelin chimeric lipid bilayer for improved therapeutic delivery.Nature communications · 2024Article
- Molecular origins of asymmetric proton conduction in the influenza M2 channel.Biophysical journal · 2023Article
- Spiers Memorial Lecture: Analysis andFaraday discussions · 2021Article
- Theoretical and experimental comparisons of simple peptide-membrane systems; towards defining the reaction space: general discussion.Faraday discussions · 2021Article
- Influenza A M2 recruits M1 to the plasma membrane: A fluorescence fluctuation microscopy study.Biophysical journal · 2021Article
- Folding and misfolding of potassium channel monomers during assembly and tetramerization.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The Role of the Membrane in Transporter Folding and Activity.Journal of molecular biology · 2021Review
- Membrane receptor activation mechanisms and transmembrane peptide tools to elucidate them.The Journal of biological chemistry · 2020Review
- Transmembrane Domain Dissociation Is Required for Hendra Virus F Protein Fusogenic Activity.Journal of virology · 2019Article
- Comparison of in vitro and in vivo oligomeric states of a wild type and mutant trimeric inner membrane multidrug transporter.Biochemistry and biophysics reports · 2018Article
- The lipid bilayer membrane and its protein constituents.The Journal of general physiology · 2018Review
- Structure and Dynamics of Membrane Proteins from Solid-State NMR.Annual review of biophysics · 2018Review
- De novo designed transmembrane peptides activating the α5β1 integrin.Protein engineering, design & selection : PEDS · 2018Article
- Perturbations of Native Membrane Protein Structure in Alkyl Phosphocholine Detergents: A Critical Assessment of NMR and Biophysical Studies.Chemical reviews · 2018Review
- Lipid bilayer composition modulates the unfolding free energy of a knotted α-helical membrane protein.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Applications of Single-Molecule Methods to Membrane Protein Folding Studies.Journal of molecular biology · 2018Review
20 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Despite significant efforts and promising progress, the understanding of membrane protein folding lags behind that of soluble proteins. Insights into the energetics of membrane protein folding have been gained from biophysical studies in membrane-mimicking environments (primarily detergent micelles). However, the development of techniques for studying the thermodynamics of folding in phospholipid bilayers remains a considerable challenge. We had previously used thiol-disulfide exchange to study the thermodynamics of association of transmembrane alpha-helices in detergent micelles; here, we extend this methodology to phospholipid bilayers. The system for this study is the homotetrameric M2 proton channel protein from the influenza A virus. Transmembrane peptides from this protein specifically self-assemble into tetramers that retain the ability to bind to the drug amantadine. Thiol-disulfide exchange under equilibrium conditions was used to quantitatively measure the thermodynamics of this folding interaction in phospholipid bilayers. The effects of phospholipid acyl chain length and cholesterol on the peptide association were investigated. The association of the helices strongly depends on the thickness of the bilayer and cholesterol levels present in the phospholipid bilayer. The most favorable folding occurred when there was a good match between the width of the apolar region of the bilayer and the hydrophobic length of the transmembrane helix. Physiologically relevant variations in the cholesterol level are sufficient to strongly influence the association. Evaluation of the energetics of peptide association in the presence and absence of cholesterol showed a significantly tighter association upon inclusion of cholesterol in the lipid bilayers.
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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.