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Methods Mol Biol. 2017;1583:7-19. doi: 10.1007/978-1-4939-6875-6_2.

Hybrid In Silico/In Vitro Approaches for the Identification of Functional Cholesterol-Binding Domains in Membrane Proteins.

Author information

1
EA-4674, Interactions Moléculaires et Systèmes Membranaires, Aix-Marseille Université, 163 Avenue de Luminy, 13288, Marseille Cedex 9, France.
2
EA-4674, Interactions Moléculaires et Systèmes Membranaires, Aix-Marseille Université, 163 Avenue de Luminy, 13288, Marseille Cedex 9, France. jacques.fantini@univ-amu.fr.

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.

KEYWORDS:

Alzheimer’s β-amyloid peptide; Cholesterol-binding motif; Langmuir monolayer; Molecular docking; Molecular dynamics simulations; Transmembrane domain

PMID:
28205163
DOI:
10.1007/978-1-4939-6875-6_2
[Indexed for MEDLINE]

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