Sensory Rhodopsin Crystal Provides First Detailed Image of Primitive Vision Mechanism

UC Irvine researchers have developed a unique crystal structure of sensory rhodopsin, a membrane protein that signals light information to cells, and for the first time are learning how it changes shape to recognize the sun's emission spectrum, providing new information on a primitive form of vision.

In addition to identifying the structure and function of this protein, the findings also provide a molecular model that eventually could enable medical researchers to design new drugs to treat a variety of diseases. These findings are being published in the journal Science as part of the Science Express Website (www.sciencexpress.org).

Hartmut Luecke, UCI professor of molecular biology and biochemistry, and fellow researchers created a three-dimensional image of the sensory rhodopsin II protein (NpSRII) to understand how it transforms when absorbing blue light, the most intense kind in the sun's emission spectrum. This highly specialized form of rhodopsin is found in salt marsh-dwelling bacteria called Natronobacterium pharaonis.

When sensory rhodopsin is activated, it sends a message through a second signaling protein, called a transducer, telling the cell how to react, by either avoiding harsh blue light or moving toward a lower-energy form of light in order to create energy.

"With our new structure, we are beginning to better understand the mechanism of spectral tuning," said Luecke, who is also a professor of physiology and biophysics. "This structure also provides a crucial step to understanding the mechanisms involved with trans-membrane cell signaling."

In capturing an image of sensory rhodopsin that absorbs blue light, the scientists measured a 1.1-Angstrom shift of a charged group deep inside the molecule. This shift turns out to be largely responsible for the change in absorption wavelength when compared with other rhodopsins.

Luecke and his team also report the discovery of a unique binding site for this signaling activity. On inspecting the protein surface, they found an exposed amino acid, tyrosine (Tyr199), in the middle of the bilayer. "We believe we have identified one of the important sites where rhodopsin interacts with its transducer protein, which will allow us to recognize the very fundamental signal transduction with these molecules," Luecke said.

While crystal structures of other protein groups are common research items, such structures of membrane proteins like rhodopsin are rare. In fact, Luecke noted, this research reveals for the first time a crystal structure of sensory rhodopsin. But structural and functional information from this protein is becoming increasingly important to understanding how G-protein coupled receptors (GPCRs) work. GPCRs, a protein group that transduces signals across cell membranes, have proven to be excellent therapeutic targets. Nearly half of all known drugs act on GPCRs. While sensory rhodopsin is not a GPCR, it provides a model for study.

Luecke and his fellow researchers plan to further explore crystal structures of rhodopsin molecules during different photocycle states in order to understand how the protein alters its shape to send messages.

In addition to Luecke, Brigitte Schobert and Janos K. Lanyi of UCI's Department of Physiology and Biophysics and Elena N. Spudich and John L. Spudich of the University of Texas Medical School, Houston, assisted in the research. The National Institutes of Health, the U.S. Department of Energy and a Welch Investigator Award provided funding.

Contact:
Tom Vasich
(949) 824-6455
tmvasich@uci.edu

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