Abstract
Membrane proteins (MPs) are essential to many organisms’ major functions. They are notorious for being difficult to isolate and study, and mimicking native conditions for studies in vitro has proved to be a challenge. Lipid nanodiscs are among the most promising platforms for MP reconstitution, but they contain a relatively labile lipid bilayer and their use requires previous protein solubilization in detergent. These limitations have led to the testing of copolymers in new types of nanodisc platforms. Polymer-encased nanodiscs and polymer nanodiscs support functional MPs and address some of the limitations present in other MP reconstitution platforms. In this review, we provide a summary of recent developments in the use of polymers in nanodiscs.
Highlights
Membrane proteins (MPs) are essential for cell homeostasis, signaling, transport, and energy production
At least 50% of current druggable targets are classified as MPs, and about half of all known small molecule drugs bind to them (Russell and Eggleston, 2000; Overington et al, 2006)
Lipid nanodiscs (LNDs) are composed of a disc-shaped phospholipid bilayer surrounded by a two-molecule belt of a membrane scaffold protein (MSP) (Figure 1B), a protein derived from apolipoprotein A1, a major component of serum high-density lipoprotein complexes (Denisov and Sligar, 2016)
Summary
MPs are essential for cell homeostasis, signaling, transport, and energy production They play critical roles in normal function and human disease, and as such they are important drug targets (Overington et al, 2006). Studies of proteins in their native environment are critical to understanding their function and regulation in organisms and cells, but details on their structures and mechanisms at the atomic and molecular level are better investigated on purified proteins under well-controlled conditions. Studies of purified MPs include expression through recombinant methods followed by extraction from membranes using detergents to produce the proteins solubilized in detergent micelles (Figure 1; Seddon et al, 2004; Hardy et al, 2018; Stroud et al, 2018). We focus on the latter, which constitute an MP platform of excellent properties that offers great potential
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