A healthy mind and body require the coordinated action of billions of tiny molecular workers called proteins. Proteins are indispensable molecules in our bodies, and each has a unique three-dimensional shape, or structure, that is well suited for its particular job. The Structural Biology Research Program is a strategic effort to help create a "picture gallery” of three-dimensional protein structures. This program supports the development of rapid, efficient, and dependable methods that can be used to determine the structure of proteins. The intent of this effort is to transform what is currently a hit-or-miss process into an organized, coordinated, systematic, and streamlined routine, helping researchers clarify the role of protein structure in health and disease.
A limiting step in the determination of protein structures is the production of sufficient quantities of pure protein samples for structure determination. Proteins that are tightly bound to the membranes of our cells have been the most difficult to study because of the technical difficulties in isolating proteins away from the membrane without destroying their structure. This program is developing new approaches to purifying ample amounts of stable protein for various investigations and applications, including for improved therapeutic drug development. Membrane proteins account for about 30% of the proteins in a cell and are one of the most important targets of drug development. Knowing the structure of a protein helps in the development of drugs with fewer side effects by allowing one to target particular protein surfaces to disrupt specific activities of the protein.
During the first phase of the Structural Biology Research Program (FY2004-2008), the Common Fund supported two Centers for Innovation in Membrane Protein Production that enabled interdisciplinary groups of scientists to develop innovative methods for producing large quantities of membrane proteins. In addition, a number of small exploratory (R21) and regular research (R01) grants were awarded to individual investigators to broaden the base of innovative ideas under development.
During the current phase of the Structural Biology Research Program (FY2009-2013), researchers are developing additional innovative approaches for membrane protein production as well as structure determination, including methodologies that can be applied to protein complexes made up of multiple protein components, such as different types of proteins. The work during this phase is occurring at the two Centers for Innovation in Membrane Protein Production as well as through additional R01 grants.