De novo design and synthesis of a small globular protein that forms a pore in lipid bilayers

We report here the design and synthesis of a native-like and pore-forming small protein (SGP) and its related analogs. SGP consists of 69 amino acid residues divided over four helical parts; 3 basic amphiphilic helices surrounding a central hydrophobic helix SGP takes a stable globular-like structure in aqueous solution. In the SGP proteins, the hydrophobic central α-helix is able to enter spontaneously into lipid bilayers and the Trp in central α-helix is located about in the middle of the alkyl chain in the outer layer of the phospholipid bilayer. The protein is also able to increase the membrane permeability with two modes of current in planar phospholipid bilayers, indicating that the spontaneous insertion of the protein into lipid bilayers, and then the formation of channel pores SGP also induced apoptosis (Apoptosis is an evolutionarily conserved form of cell suicide).