Reconstitution of Membrane Proteins into Model Membranes: Seeking Better Ways to Retain Protein Activities

Abstract

The function of any given biological membrane is determined largely by the specific set of integral membrane proteins embedded in it, and the peripheral membrane proteins attached to the membrane surface. The activity of these proteins, in turn, can be modulated by the phospholipid composition of the membrane. The reconstitution of membrane proteins into a model membrane allows investigation of individual features and activities of a given cell membrane component. However, the activity of membrane proteins is often difficult to sustain following reconstitution, since the composition of the model phospholipid bilayer differs from that of the native cell membrane. This review will discuss the reconstitution of membrane protein activities in four different types of model membrane—monolayers, supported lipid bilayers, liposomes and nanodiscs, comparing their advantages in membrane protein reconstitution. Variation in the surrounding model environments for these four different types of membrane layer can affect the three-dimensional structure of reconstituted proteins and may possibly lead to loss of the proteins activity. We also discuss examples where the same membrane proteins have been successfully reconstituted into two or more model membrane systems with comparison of the observed activity in each system. Understanding of the behavioral changes for proteins in model membrane systems after membrane reconstitution is often a prerequisite to protein research. It is essential to find better solutions for retaining membrane protein activities for measurement and characterization in vitro.

Shedding light on the puzzle of drug-membrane interactions: Experimental techniques and molecular dynamics simulations

“…There are several experimentally used membrane models that allow proteins to be inserted, such as monolayers, supported lipid bilayers and liposomes [259]. However, the protein activity may be hard to preserve after inserting them into the models [259].…”

Fast Photochemical Oxidation of Proteins Maps the Topology of Intrinsic Membrane Proteins: Light-Harvesting Complex 2 in a Nanodisc

“…Thus, a Nanodisc provides a simple and robust means for rendering target membrane proteins in aqueous buffer while keeping the protein in a native-like bilayer environment. 11 …”

Physicochemical characterization of artificial nanoerythrosomes derived from erythrocyte ghost membranes

“…Because of the complex and variable composition of biological membranes, they are often substituted with model membranes for primal investigations. Such model membranes can be simple or more complex artificial lipid bilayers, or even purified membranes prepared from live cells [5][6][7].…”