"A novel mRNA display platform to evolve stable mutants of human membrane proteins for structure determination by X-ray crystallography"
Institution: Columbia University Medical Center
Principal Investigator: Dr. Filippo Mancia
Research Category: Basic Science
Every interaction between a cell and its surroundings occurs through the cell’s membrane, a water-impermeable barrier that surrounds it. These interactions are often mediated by proteins dissolved in the membrane, which are therefore crucial to the cell’s operation and are the most common drug targets. Despite their relevance to human health, knowledge of the atomic structure of membrane proteins lags far behind that of their soluble counterparts due to numerous difficulties posed in their production, purification and crystallization—all pre-requisites for structure determination by x-ray crystallography, the most powerful and successful technique available to date for structure determination to atomic resolution. The objective of this proposal is to develop a method to generate billions of mutations in human membrane proteins and identify those few that increase their probability of yielding ordered crystals. Success relies on being able to link the stable protein variant to its own genetic information. The methods we propose to develop could yield a powerful new tool to substantially increase the rate at which we shed light on the atomic structure of human membrane proteins by x-ray crystallography, leading for further much-awaited progress in our understanding and treatment of disease.
The above project description has been supplied by the Principal Investigator