Compositions and Methods for Producing Recombinant Membrane-Associated Proteins
Inventors: Tarmo Roosild, Jason Greenwald, Senyon Choe, Roland Riek, Mark Vega
Potential Uses: Research Tool, Drug Discovery and Development, Membrane Protein Production
A 'partner' molecule called Mistic makes widespread production of large quantities of membrane proteins possible for the first time, allowing scientists to determine their atomic structure and design drugs that interfere with disease processes involving crucial proteins such as ion channels and GPCRs.
Membrane proteins are crucially important in medical research and drug discovery, but until now human membrane proteins have been virtually impossible to produce in large enough amounts to study. Out of approximately 10,000 human genes dedicated to integral membrane proteins, such as receptors and ion channels, only a small handful of proteins have been made available from natural sources in the quality and quantity needed to study them successfully in isolation.
The discovery of Mistic, which facilitates the integration of cloned membrane proteins into the E. coli cell membrane, gives medical researchers a new tool that could revolutionize membrane biology.
Mistic is an unusual Bacillus subtilis integral membrane protein, with a structure that consists of a bundle of four helices that fold autonomously into place within the cell membrane, bypassing the cellular translocon machinery. This self-integrating, or auto-inserting, ability of Mistic facilitates the rest of the molecule, the "cargo" protein, to undergo the folding and integration process.
Mistic allows scientists for the first time to produce large quantities of crucial membrane proteins for structural study or therapeutic research, such as ion channels and the vast family of receptors called G-protein coupled receptors (GPCRs). More than half the blockbuster drugs in the pharmaceutical industry target these two classes of proteins.
Salk researchers have successfully created dozens of such important human membrane proteins in the cell membrane of E. coli using Mistic. _ In addition, experiments suggest that Mistic can be used for high-level production of other membrane proteins in their native conformations, including many eukaryotic proteins that have previously been intractable to recombinant bacterial expression.
Patent Status: U.S. Patent Application Published as US-2006-0211087 A1
Publications: Science 307 1317-1321
License Terms: Exclusive or Non-Exclusive Licenses available by Field of Use
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