ArticleProceedings of the National Academy of Sciences of the United States of America2012
Membrane physical properties influence transmembrane helix formation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. 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, 80 citations in OpenAlex.
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- Circular-Dichroism and Synchrotron-Radiation Circular-Dichroism Spectroscopy as Tools to Monitor Protein Structure in a Membrane Environment.Methods in molecular biology (Clifton, N.J.) · 2026Article
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- Unlocking the power of membrane biophysics: enhancing the study of antimicrobial peptides activity and selectivity.Biophysical reviews · 2025Review
- Cholesterol inhibits assembly and oncogenic activation of the EphA2 receptor.Communications biology · 2025Article
- Neutron spin echo shows pHLIP is capable of retarding membrane thickness fluctuations.Biochimica et biophysica acta. Biomembranes · 2024Article
- Cholesterol inhibits assembly and activation of the EphA2 receptor.bioRxiv : the preprint server for biology · 2024Article
- Aiming the magic bullet: targeted delivery of imaging and therapeutic agents to solid tumors by pHLIP peptides.Frontiers in pharmacology · 2024Review
- Promoting the activity of a receptor tyrosine phosphatase with a novel pH-responsive transmembrane agonist inhibits cancer-associated phenotypes.Protein science : a publication of the Protein Society · 2023Article
- Increasing the Realism ofJournal of chemical theory and computation · 2022Article
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- CaProtein science : a publication of the Protein Society · 2022Article
- The interaction of steroids with phospholipid bilayers and membranes.Biophysical reviews · 2022Review
- Roles of key residues and lipid dynamics reveal pHLIP-membrane interactions at intermediate pH.Biophysical journal · 2021Article
- Single-molecule fluorescence vistas of how lipids regulate membrane proteins.Biochemical Society transactions · 2021Review
- pH-triggered pore-forming peptides with strong composition-dependent membrane selectivity.Biophysical journal · 2021Article
- Effect of DMSO on the Mechanical and Structural Properties of Model and Biological Membranes.Biophysical journal · 2020Article
- Tumor-Targeted, Cytoplasmic Delivery of Large, Polar Molecules Using a pH-Low Insertion Peptide.Molecular pharmaceutics · 2020Article
- Article
- The conical shape of DIM lipids promotesProceedings of the National Academy of Sciences of the United States of America · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The pHLIP peptide has three states: (I) soluble in aqueous buffer, (II) bound to the bilayer surface at neutral pH, and (III) inserted as a transmembrane (TM) helix at acidic pH. The membrane insertion of pHLIP at low pH can be used to target the acidic tissues characteristic of different diseases, such as cancer. We find that the α-helix content of state II depends on lipid acyl chain length but not cholesterol, suggesting the helicity of the bound state may be controlled by the bilayer elastic bending modulus. Experiments with the P20G variant show the proline residue in pHLIP reduces the α-helix content of both states II and III. We also observe that the membrane insertion pKa is influenced by membrane physical properties, following a biphasic pattern similar to the membrane thickness optima observed for the function of eukaryotic membrane proteins. Because tumor cells exhibit altered membrane fluidity, we suggest this might influence pHLIP tumor targeting. We used a cell insertion assay to determine the pKa in live cells, observing that the properties in liposomes held in the more complex plasma membrane. Our results show that the formation of a TM helix is modulated by both the conformational propensities of the peptide and the physical properties of the bilayer. These results suggest a physical role for helix-membrane interactions in optimizing the function of more complex TM proteins.
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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.