Abstract
In eukaryotic cells, cholesterol is an important regulator of a broad range of membrane proteins, including receptors, transporters, and ion channels. Understanding how cholesterol interacts with membrane proteins is a difficult task because structural data of these proteins complexed with cholesterol are scarce. Here, we describe a dual approach based on in silico studies of protein–cholesterol interactions, combined with physico-chemical measurements of protein insertion into cholesterol-containing monolayers. Our algorithm is validated through careful analysis of the effect of key mutations within and outside the predicted cholesterol-binding site. Our method is illustrated by a complete analysis of cholesterol-binding to Alzheimer’s β-amyloid peptide, a protein that penetrates the plasma membrane of brain cells through a cholesterol-dependent process.
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References
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Acknowledgments
We would like to thank Henri Chahinian, Francisco Barrantes, and Nouara Yahi for their constant support and encouragement, and for valuable discussions.
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Di Scala, C., Fantini, J. (2017). Hybrid In Silico/In Vitro Approaches for the Identification of Functional Cholesterol-Binding Domains in Membrane Proteins. In: Gelissen, I., Brown, A. (eds) Cholesterol Homeostasis. Methods in Molecular Biology, vol 1583. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6875-6_2
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DOI: https://doi.org/10.1007/978-1-4939-6875-6_2
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