ArticleProceedings of the National Academy of Sciences of the United States of America2009
The transition state for integral membrane protein folding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 67 citations in OpenAlex.
- Single Molecule Force Spectroscopy to Probe Intermediates and Energetics of Membrane Protein Folding.Chemical reviews · 2026Review
- Probing the energy barriers and stages of membrane protein unfolding using solid-state NMR spectroscopy.Science advances · 2024Article
- The full spectrum of SLC22 OCT1 mutations illuminates the bridge between drug transporter biophysics and pharmacogenomics.Molecular cell · 2024Article
- Steric trapping strategy for studying the folding of helical membrane proteins.Methods (San Diego, Calif.) · 2024Review
- 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
- Methods to study folding of alpha-helical membrane proteins in lipids.Open biology · 2022Review
- How lipids affect the energetics of co-translational alpha helical membrane protein folding.Biochemical Society transactions · 2022Review
- Free-energy changes of bacteriorhodopsin point mutants measured by single-molecule force spectroscopy.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- The high-energy transition state of the glutamate transporter homologue GltPh.The EMBO journal · 2021Article
- Watching helical membrane proteins fold reveals a common N-to-C-terminal folding pathway.Science (New York, N.Y.) · 2019Article
- 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
- Kinetic stability of membrane proteins.Biophysical reviews · 2017Review
- A growing toolbox of techniques for studying β-barrel outer membrane protein folding and biogenesis.Biochemical Society transactions · 2016Review
- Kinetics of peptide folding in lipid membranes.Biopolymers · 2015Review
- Cooperative folding of a polytopic α-helical membrane protein involves a compact N-terminal nucleus and nonnative loops.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Peptide Folding in Translocon-Like Pores.The Journal of membrane biology · 2015Article
- The safety dance: biophysics of membrane protein folding and misfolding in a cellular context.Quarterly reviews of biophysics · 2015Article
- Mechanistic studies of the biogenesis and folding of outer membrane proteins in vitro and in vivo: what have we learned to date?Archives of biochemistry and biophysics · 2014Review
- Bacteriorhodopsin folds through a poorly organized transition state.Journal of the American Chemical Society · 2014Article
- Predictive energy landscapes for folding α-helical transmembrane proteins.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
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2 authors at 1 institution in 1 country.
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Abstract
Biology relies on the precise self-assembly of its molecular components. Generic principles of protein folding have emerged from extensive studies on small, water-soluble proteins, but it is unclear how these ideas are translated into more complex situations. In particular, the one-third of cellular proteins that reside in biological membranes will not fold like water-soluble proteins because membrane proteins need to expose, not hide, their hydrophobic surfaces. Here, we apply the powerful protein engineering method of Phi-value analysis to investigate the folding transition state of the alpha-helical membrane protein, bacteriorhodopsin, from a partially unfolded state. Our results imply that much of helix B of the seven-transmembrane helical protein is structured in the transition state with single-point alanine mutations in helix B giving Phi values >0.8. However, residues Y43 and T46 give lower Phi values of 0.3 and 0.5, respectively, suggesting a possible reduction in native structure in this region of the helix. Destabilizing mutations also increase the activation energy of folding, which is accompanied by an apparent movement of the transition state toward the partially unfolded state. This apparent transition state movement is most likely due to destabilization of the structured, unfolded state. These results contrast with the Hammond effect seen for several water-soluble proteins in which destabilizing mutations cause the transition state to move toward, and become closer in energy to, the folded state. We thus introduce a classic folding analysis method to membrane proteins, providing critical insight into the folding transition state.
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