Membrane Scaffold Protein 2N2

Research area: Cell Struc

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.

Nanodisc technology is an approach rendering 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 that mimics the function of Apolipoprotein A-1 (ApoA-1).

Membrane Scaffold Protein 2N2 has been used in enzyme-linked immunosorbent assay (ELISA) and for reconstitution of human β3 homopentameric gamma-aminobutyric acid type A receptor (GABAAR) in nanodiscs.

Scaffold proteins play a crucial role in providing specificity to the mitogen-activated protein kinase (MAPK) pathway, which is essential for normal cellular functions and development. They help regulate the localization of MAPK components, allowing for targeted modulation of cellular responses without affecting global MAPK activity.

Nanodisc technology, and many of its uses, are covered by the following patents held by the University of Illinois.

• 7,691,414 Membrane scaffold proteins
• 7,662,410 Membrane scaffold proteins and embedded membrane proteins
• 7,622,437 Tissue factor compositions and methods
• 7,592,008 Membrane scaffold proteins
• 7,575,763 Membrane scaffold proteins and tethered membrane proteins
• 7,083,958 Membrane scaffold proteins
• 7,048,949 Membrane scaffold proteins