ArticleeLife2016
Mutational scanning reveals the determinants of protein insertion and association energetics in the plasma membrane.
Article in eLife, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 82 citations in OpenAlex.
- Molecular dynamics simulations of intrinsically disordered protein regions enable biophysical interpretation of variant-effect predictors.HGG advances · 2026Article
- Membrane-Based Assembly and Interactions in Immune Receptors.Chemical reviews · 2026Review
- Membrane insertion and dimerization of glycophorin-A mutations studied by free energy simulations.Biophysical journal · 2026Article
- The sequence and structural integrity of the SARS-CoV-2 Spike protein transmembrane domain is crucial for viral entry.Communications biology · 2025Article
- High-throughput discovery of transmembrane helix dimers from human single-pass membrane proteins with TOXGREEN sort-seq.PNAS nexus · 2025Article
- One-shot design elevates functional expression levels of a voltage-gated potassium channel.Protein science : a publication of the Protein Society · 2024Article
- Modeling membrane geometries implicitly in Rosetta.Protein science : a publication of the Protein Society · 2024Article
- Deep mutational scanning reveals transmembrane features governing surface expression of the B cell antigen receptor.Frontiers in immunology · 2024Article
- ProteinGym: Large-Scale Benchmarks for Protein Design and Fitness Prediction.bioRxiv : the preprint server for biology · 2023Article
- Computational design of BclxL inhibitors that target transmembrane domain interactions.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Integrating deep mutational scanning and low-throughput mutagenesis data to predict the impact of amino acid variants.GigaScience · 2022Article
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- Differential Pathomechanisms of Desmoglein 1 Transmembrane Domain Mutations in Skin Disease.The Journal of investigative dermatology · 2022Article
- Spiers Memorial Lecture: Analysis andFaraday discussions · 2021Article
- Climbing Up and Down Binding Landscapes through Deep Mutational Scanning of Three Homologous Protein-Protein Complexes.Journal of the American Chemical Society · 2021Article
- Artificial Intelligence, Machine Learning and Deep Learning in Ion Channel Bioinformatics.Membranes · 2021Review
- Diverse Scientific Benchmarks for Implicit Membrane Energy Functions.Journal of chemical theory and computation · 2021Article
- Membrane proteins enter the fold.Current opinion in structural biology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Insertion of helix-forming segments into the membrane and their association determines the structure, function, and expression levels of all plasma membrane proteins. However, systematic and reliable quantification of membrane-protein energetics has been challenging. We developed a deep mutational scanning method to monitor the effects of hundreds of point mutations on helix insertion and self-association within the bacterial inner membrane. The assay quantifies insertion energetics for all natural amino acids at 27 positions across the membrane, revealing that the hydrophobicity of biological membranes is significantly higher than appreciated. We further quantitate the contributions to membrane-protein insertion from positively charged residues at the cytoplasm-membrane interface and reveal large and unanticipated differences among these residues. Finally, we derive comprehensive mutational landscapes in the membrane domains of Glycophorin A and the ErbB2 oncogene, and find that insertion and self-association are strongly coupled in receptor homodimers.
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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.