"Understanding how T cells draw from all the information embedded in the human genome to determine how to respond to an immune challenge like a virus, tumor cell, or transplant is an opportunity to study the mechanisms of health and disease," added Salomon, "and to do this at the level of protein structures in this new collaboration with the JCSG is a remarkable opportunity to advance translation biology and medicine."

The scientists will use genomic, biochemical, and functional research in combination with structural studies to forge new inroads in the field.

Membrane Protein Structures

The new grants also support nine centers-two of which are based at The Scripps Research Institute-for determining membrane protein structures. Membrane proteins, which are embedded in the membranes of our cells, are important because they enable our nerves, muscles, and even hormones to do their jobs. Currently, however, scientists can't easily visualize their three-dimensional shapes to understand how these proteins function.

The Scripps Research Institute center led by Stevens, Cherezov, Kuhn, Rosen, and W-thrich will focus on a special class of human membrane proteins called G protein-coupled receptors (GPCRs), signaling molecules that span the membranes of cells, "sensing" chemical messages outside the cells and converting them into action within the cell. GPCRs are the largest family of proteins in the human genome.

"Our fundamental understanding of GPCR molecular recognition and signaling is still in the early stages," said Stevens. "Through the creation of the GPCR Network center, we will work directly with the GPCR community on improving our basic understanding of receptor structure and function using a variety of biophysical techniques including NMR, HDX, and X-ray crystallography, as well as computational and chemical screening techniques. Only a few GPCR structures in their inactive state have been solved to date and the basic understanding of this key membrane protein class will change drastically in the next five years with the NIH funding."

In a separate group, Chang, Rees, and Stowell will focus on a class of proteins called transporters-a type of large protein that resides in the cell membrane and moves other molecules in and out. Transporters are vital to the biology of all cells and a variety of diseases occur when these processes are perturbed or disrupted, as in several genetic disorders. In addition, cancer cells resist chemotherapy by using these transporters, and bacterial cells use them to resist antibiotics.

"We actually have very good drugs to fight cancer and to kill bacteria," said Chang. "[But] they can't always get into the cells to work."

This new center, dubbed TransportPDB, aims to develop a comprehensive and efficient approach for pursuing the high-resolution x-ray crystal structures of several transporters that PSI scientists have selected as important in biomedicine.

Source: Scripps Research Institute