Researcher Discovers Shape of Proteins Important in Neurological Disorders
Dopamine is an essential "neurotransmitter", conveying important signals from one cell in the brain to another. Disruption of these signals initiated by dopamine can lead to schizophrenia, Parkinson’s disease, or drug addiction. The D3R protein is one of five dopamine receptor subtypes that bind dopamine to mediate cellular communication and is a primary target for the development of drugs to treat these conditions. Frequently, however, drugs that affect D3R can also affect the other dopamine receptor proteins and causing unwanted side effects. The Joint Center for Integral Membrane Protein Technologies-Complexes (JCIMPT-Complexes) at the Scripps Research Institute headed by Dr. Raymond C. Stevens, funded in part by the Common Fund’s Structural Biology program, has determined the three-dimensional shape of D3R, described in the November 19th advance online issue of the journal Science. This shape reveals subtle differences between D3R and the closely related protein D2R, which may assist researchers in designing effective D3R-specific drugs with fewer side effects. The research finding is particularly significant because D3R is a type of "membrane protein," a protein that is embedded in the viscous lipid environment surrounding a cell, making it challenging to isolate the protein to determine its shape. This finding comes soon after Dr. Stevens’ discovery of the shape of CXCR4, a protein important for HIV infection and cancer. By using methods similar to those pioneered by JCIMPT-Complexes and other research labs within the Structural Biology program, scientists have the potential to determine the structure of Image courtesy of Dr. Raymond Stevens many more proteins implicated in human diseases and develop more targeted therapeutic drugs.