A team of scientists from The Scripps Research Institute, collaborating with members of the drug discovery company Receptos, has created the first high-resolution virtual image of cellular structures called S1P1 receptors, which are critical in controlling the onset and progression of multiple sclerosis and other diseases. This new molecular map is already pointing researchers toward promising new paths for drug discovery and aiding them in better understanding how certain existing drugs work.
The molecular structure, described in the February 17, 2012 issue of the journal Science, is unique as the first-ever-to-be-determined lipid G protein-coupled receptor (GPCR). Molecules of this type play important roles in everything from cancer to metabolism, and this recent success should pave the way for researchers to establish the structures of other family members.
“There’s something special about the S1P1 receptor,” said Hugh Rosen, MD, PhD, a Scripps Research chemical biologist who co-led the work with Raymond Stevens, PhD, a structural biologist also from The Scripps Research Institute. “The biological consequences of even small changes with this receptor are profound. Understanding its structure provides clues about fundamental processes important in both health and disease.”
“Being able to finally look at a lipid GPCR and the occluded cell surface binding pocket was a surprise but explains many of the issues we wondered about,” said Stevens. “It is likely that other members of this subfamily will have a similar protein architecture.”