ArticleProceedings of the National Academy of Sciences of the United States of America2015
Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 65 citations in OpenAlex.
- The Shape of Things to Come: α-Helical Membrane Protein Folding on the Ribosome.Chemical reviews · 2026Review
- Membrane Protein Folding and Biogenesis: Insights from Single-Molecule Force Spectroscopy.Chemical reviews · 2026Review
- Linking multipoint folding and stability with functional regulation in the mitochondrial transmembrane β-barrel Sam50.Nature communications · 2026Article
- Single Molecule Force Spectroscopy to Probe Intermediates and Energetics of Membrane Protein Folding.Chemical reviews · 2026Review
- Oxidative photocatalysis on membranes triggers non-canonical pyroptosis.Nature communications · 2024Article
- Steric trapping strategy for studying the folding of helical membrane proteins.Methods (San Diego, Calif.) · 2024Review
- Folding speeds of helical membrane proteins.Biochemical Society transactions · 2024Review
- Interpreting the molecular mechanisms of disease variants in human transmembrane proteins.Biophysical journal · 2023Article
- Factors That Control the Force Needed to Unfold a Membrane Protein in Silico Depend on the Mode of Denaturation.International journal of molecular sciences · 2023Article
- Observation of Strong Synergy in the Interfacial Water Response of Binary Ionic and Nonionic Surfactant Mixtures.The journal of physical chemistry letters · 2022Article
- Methods to study folding of alpha-helical membrane proteins in lipids.Open biology · 2022Review
- How physical forces drive the process of helical membrane protein folding.EMBO reports · 2022Review
- Untangling the complexity of membrane protein folding.Current opinion in structural biology · 2022Review
- Lipid bilayer induces contraction of the denatured state ensemble of a helical-bundle membrane protein.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Cell-Free Synthesis Strategies to Probe Co-translational Folding of Proteins Within Lipid Membranes.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Cys-labeling kinetics of membrane protein GlpG: a role for specific SDS binding and micelle changes?Biophysical journal · 2021Article
- A complex unfolding pathway of α-helical membrane proteins in SDS-containing micelles.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
- Article
- The high-energy transition state of the glutamate transporter homologue GltPh.The EMBO journal · 2021Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Despite the ubiquity of helical membrane proteins in nature and their pharmacological importance, the mechanisms guiding their folding remain unclear. We performed kinetic folding and unfolding experiments on 69 mutants (engineered every 2-3 residues throughout the 178-residue transmembrane domain) of GlpG, a membrane-embedded rhomboid protease from Escherichia coli. The only clustering of significantly positive ϕ-values occurs at the cytosolic termini of transmembrane helices 1 and 2, which we identify as a compact nucleus. The three loops flanking these helices show a preponderance of negative ϕ-values, which are sometimes taken to be indicative of nonnative interactions in the transition state. Mutations in transmembrane helices 3-6 yielded predominantly ϕ-values near zero, indicating that this part of the protein has denatured-state-level structure in the transition state. We propose that loops 1-3 undergo conformational rearrangements to position the folding nucleus correctly, which then drives folding of the rest of the domain. A compact N-terminal nucleus is consistent with the vectorial nature of cotranslational membrane insertion found in vivo. The origin of the interactions in the transition state that lead to a large number of negative ϕ-values remains to be elucidated.
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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.