Artificial membrane-like environments for in vitro studies of purified G-protein coupled receptors

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Abstract

Functional reconstitution of transmembrane proteins remains a significant barrier to their biochemical, biophysical, and structural characterization. Studies of seven-transmembrane G-protein coupled receptors (GPCRs) in vitro are particularly challenging because, ideally, they require access to the receptor on both sides of the membrane as well as within the plane of the membrane. However, understanding the structure and function of these receptors at the molecular level within a native-like environment will have a large impact both on basic knowledge of cell signaling and on pharmacological research. The goal of this article is to review the main classes of membrane mimics that have been, or could be, used for functional reconstitution of GPCRs. These include the use of micelles, bicelles, lipid vesicles, nanodiscs, lipidic cubic phases, and planar lipid membranes. Each of these approaches is evaluated with respect to its fundamental advantages and limitations and its applications in the field of GPCR research. This article is part of a Special Issue entitled: Membrane protein structure and function.

Graphical abstract

Highlights

► Reconstitution into native membrane-like environments is needed for quantitative biophysical studies of GPCRs. ► Six classes of membrane mimics are reviewed and evaluated for GPCR reconstitution. ► Classes reviewed here include micelles, bicelles, nanodiscs, lipid vesicles, planar lipid membranes, and lipidic cubic phases. ► Theoretical advantages and limitations for each reconstitution system are discussed. ► Examples of applications are provided.

Abbreviations

GPCR
G-protein coupled receptor
SUV
small unilamellar vesicle
GUV
giant unilamellar vesicle
MSP
membrane scaffold protein
PLM
planar lipid membrane

Keywords

GPCR reconstitution
Bicelle
Nanodisc
Giant unilamellar vesicle
Planar lipid membrane
Lipidic cubic phase

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This article is part of a Special Issue entitled: Membrane protein structure and function.