GRAND RAPIDS, Mich., July 22, 2015 /PRNewswire/ -- Using the brightest X-ray laser in the world, scientists have determined the structure of a molecular complex that is responsible for regulating vital physiological functions, and that serves as a major pharmacological drug target.
The new findings provide scientists with a roadmap for more selectively targeting pathways for drug treatment, which may lead to more effective therapies with fewer side effects for diseases such as cancer, heart disease and neurodegenerative disorders. The study, Crystal structure of rhodopsin bound to arrestin determined by femtosecond X-ray laser, was published today in the journal Nature.
For the last decade, a team led by Van Andel Research Institute's (VARI) H. Eric Xu, Ph.D., the paper's senior author, has worked to unravel the structure of a complex made up of a signaling protein called arrestin and a G protein-coupled receptor (GPCR) called rhodopsin. Given their central roles in cellular communication, GPCRs are major targets in the development of new therapies and account for about 40 percent of current drug targets.
Arrestin, as well as other signaling proteins known as G proteins, link up with GPCRs to convey important instructions for many essential physiological functions, such as growth and hormone regulation. G protein and arrestin pathways are physiologically distinct; GPCR drugs that selectively modulate one pathway are often preferred as they can have better therapeutic benefits with fewer undesirable side effects than non-selective drugs.
"Arrestin and G proteins are the yin and the yang of regulating GPCR function," Xu said. "In the realm of drug development, a detailed understanding of the structure, interaction and function of each of these groups of proteins is vital to developing effective therapies. The more specific the interaction, the better the drugs tend to work while also lowering the chance of side effects."
The X-ray laser work was conducted at the Department of Energy's SLAC National Accelerator Laboratory, which is operated by Stanford University. Xu and his team utilized the facility's Linac Coherent Light Source, the world's first hard X-ray free electron laser, to generate the first three-dimensional map of arrestin while it was linked with a GPCR.
The work was conducted by Xu's laboratory at VARI along with VARI's Karsten Melcher, Ph.D., and collaborators across the globe.
For more information, please see the full release: http://www.vai.org/home/NewsRoom/press-release-7-22-15
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SOURCE Van Andel Institute