Transmembrane proteins are essential part of numerous cell processes, however, the purification and structure determination of transmembrane proteins remains challenging and typically requires detergents that partially substitute membrane environment. Recently, a membrane nanodisc has been developed to over come these difficulties and provide a natural lipid environment. This attractive biotechnological tool consists of a natural bilayer patch stabilized by a membrane scaffold proteins (MSP) such as modified version of human apolipoprotein [1]. Despite the nanodisc’s success in isolation, purification, crystallographic and NMR studies of transmembrane proteins, the main limitation of its use is size determined by fixed size of MSP that cannot be altered easily and thus reducing the potential utilization of membrane nanodiscs.
We present a dozen of designed sequences for amphiphilic helices that can be used as a repeating unit for MSPs whose length could be easily altered by addition of removal of the helices and thereby modify the diameter of nanodisc. Our coarse-grained simulations demonstrated that the designed helices posses necessary perpendicular orientation on the membrane edge and thus are likely to form a novel model on membrane nanodisc with so called protein fence structure. In this structure, helices tend to orient perpendicularly to the membrane and do not remain parallel to the membrane as predicted for double-belt structure [2].