ArticleThe journal of physical chemistry letters2016
Specific Binding of Cholesterol to C99 Domain of Amyloid Precursor Protein Depends Critically on Charge State of Protein.
Article in The journal of physical chemistry letters, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- From mechanistic modeling to AI-driven design: computational strategies for targeting the γ-secretase complex.Briefings in bioinformatics · 2026Review
- Salidroside mitigates cognitive deficits in AlClFrontiers in behavioral neuroscience · 2026Article
- Transient cholesterol interactions with the amyloid precursor protein involved in Alzheimer's disease pathogenesis.Biophysical reviews · 2025Review
- Cholesterol and Lipid Rafts in the Biogenesis of Amyloid-β Protein and Alzheimer's Disease.Annual review of biophysics · 2024Review
- Cholesterol-dependent amyloid β production: space for multifarious interactions between amyloid precursor protein, secretases, and cholesterol.Cell & bioscience · 2023Review
- Membrane-induced tau amyloid fibrils.Communications biology · 2023Article
- Review
- White matter injury, cholesterol dysmetabolism, and APP/Abeta dysmetabolism interact to produce Alzheimer's disease (AD) neuropathology: A hypothesis and review.Frontiers in aging neuroscience · 2023Article
- Formation of extramembraneProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Specific Mutations in the Cholesterol-Binding Site of APP Alter Its Processing and Favor the Production of Shorter, Less Toxic Aβ Peptides.Molecular neurobiology · 2022Article
- Cholesterol as a key player in amyloid β-mediated toxicity in Alzheimer's disease.Frontiers in molecular neuroscience · 2022Review
- Effect of Cholesterol on C99 Dimerization: Revealed by Molecular Dynamics Simulations.Frontiers in molecular biosciences · 2022Article
- Role of cholesterol in substrate recognition by [Formula: see text]-secretase.Scientific reports · 2021Article
- Direct Observation of Cholesterol Dimers and Tetramers in Lipid Bilayers.The journal of physical chemistry. B · 2021Article
- Amyloid Oligomers: A Joint Experimental/Computational Perspective on Alzheimer's Disease, Parkinson's Disease, Type II Diabetes, and Amyotrophic Lateral Sclerosis.Chemical reviews · 2021Review
- Impact of Cholesterol Concentration and Lipid Phase on Structure and Fluctuation of Amyloid Precursor Protein.The journal of physical chemistry. B · 2020Article
- M2 amphipathic helices facilitate pH-dependent conformational transition in influenza A virus.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- 27-Hydroxycholesterol Promotes the Transfer of Astrocyte-Derived Cholesterol to Neurons in Co-cultured SH-SY5Y Cells and C6 Cells.Frontiers in cell and developmental biology · 2020Article
- Exploring the impact of proteins on the line tension of a phase-separating ternary lipid mixture.The Journal of chemical physics · 2019Article
- Characterization of Lipid-Protein Interactions and Lipid-Mediated Modulation of Membrane Protein Function through Molecular Simulation.Chemical reviews · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Recent NMR chemical shift measurements of the 99 residue C-terminal fragment of amyloid precursor protein (APP-C99) in the presence of cholesterol provide evidence of binary complex formation between C99 and cholesterol in membrane mimetic environments. It has also been observed that the production of Aβ protein is enhanced under conditions of high cholesterol concentration. In this study, we investigated the impact of the charge state of C99 on the structure and stability of the C99-cholesterol complex. We observed that the binding of C99 to cholesterol depends critically on the charge state of Glu 693 (E22) and Asp 694 (D23). Evaluation of the pKa values of the Asp and Glu side chains suggests that these residues may be predominantly neutral in existing experimental observations of a stable C99-cholesterol complex at lower pH (characteristic of the endosomal environment), while binding is destabilized near neutral pH (characteristic of the cytoplasm). These observations suggest that specific binding of cholesterol to C99 is a sensitive function of the pH encountered in vivo, with key E22 and D23 residues serving as a "pH switch" controlling C99-cholesterol binding.
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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.