Nanodisc technology is an approach to render membrane proteins soluble in aqueous solutions in a native-like bilayer environment, where the membrane proteins remain stable and active. The Nanodisc concept is derived from high density lipoprotein (HDL) particles and their primary protein component, apolipoprotein. The Nanodisc is a non-covalent structure of phospholipid bilayer and membrane scaffold protein (MSP), a genetically engineered protein, which mimics the function of Apolipoprotein A-1 (ApoA-1).
The first MSP, MSP1, was engineered with its sequence based on the sequence of A-1, but without the globular N-terminal domain of native A-1. The Membrane Scaffold Protein 1D1 (MSP1D1) variant of MSP1 deletes the first 11 amino acids in the Helix 1 portion (referred to as “H0.5” in the accompanying figure) of the original MSP1 sequence. Membrane Scaffold Protein 2N2 (MSP 2N2) is a fusion of MSP1D1 and another MSP variant, MSP1D2. MSP1D2 deletes the first 22 amino acids of the original MSP sequence (i.e. the entire H1 segment). In MSP2N2, a GT linker connects MSP1D1 and MSP1D2.
