- Proteins Controlled by Light
UNIVERSITY PARK, Pa., & DALLAS, Oct. 16, 2008 -- Scientists have discovered a way to use light to control the activity of certain proteins, which they said could one day let them turn off disease-causing aspects of proteins in cells.
"This is one of the first examples of someone successfully controlling the activity of a protein using light," said Stephen Benkovic, Pennsylvania State University Evan Pugh Professor of Chemistry and one of the research team's leaders. "The technology one day could be expanded to have multiple uses, including the ability to turn off the activities of some disease-causing proteins in the cell."
In their experiment, researchers from Penn State and the University of Texas Southwestern Medical Center (UTSMC) in Dallas designed a hybrid protein by inserting a light-sensing protein from an oat plant into an enzyme -- a type of protein that catalyzes biochemical reactions -- from the bacterium E. coli. After engineering the two components together, the researchers found that the enzyme's activity could be manipulated by shining a light on the light-sensing protein, which the scientists refer to as a "domain."
The scientists attached a light-sensing protein (sensor) from the oat plant to an enzyme from E. coli. When they shined white light (stimulus) on the sensor, the enzyme's activity increased (output). (Image: Benkovic lab, Penn State)
"The technology works like a light switch," said Benkovic. "When we shine a light on the light-sensing domain, the enzyme's activity increases, and when we shut the light off, the enzyme's activity decreases."
According to Jeeyeon Lee, a postdoctoral scholar in the Penn State department of chemistry, the team had to consider a number of factors when designing the hybrid protein, including the protein's shape, or what is referred to as its conformation. "The conformation of a protein is important in determining its function," she said. "Without the proper conformation, our protein would not have responded to the light."
Another important factor that the team had to consider was the proper location on the enzyme into which the light-sensing protein from the oat plant would be inserted. Vishal Nashine, also a postdoctoral scholar in the chemistry department, said the team was surprised to find that the switch worked only when they attached the light-sensing domain to the enzyme at a particular site. The switch did not operate when they attached the molecule to other locations on the enzyme.
"The fact that the switch worked only when the light-sensing domain was attached to the enzyme at a specific site suggests that a unique network is active at that site through which signals, such as those responding to light, are transmitted," he said.
The successful site was located, among more than a hundred different possibilities, using a computational algorithm called the Statistical Coupling Analysis (SCA), which was pioneered by Rama Ranganathan, a professor of pharmacology at UTSMC.
The team's future research will investigate how the signal triggered by the light was transmitted from the light-sensing domain to the enzyme. "It is not yet clear how this process works," said Benkovic. "So far, the effect has been small, but we plan to optimize the technology to see if we can use light to modulate the enzyme's activity in alternative ways."
The team's results will appear in the Oct. 17 issue of the journal Science; the article's Penn State authors include Lee and Nashine. Authors from the UTSMC include Ranganathan, who is one of its lead authors; William Russ, an assistant professor of pharmacology who was responsible for locating the site on the enzyme into which the light-sensing protein was successfully inserted; and assistant professor of pharmacology Madhusudan Natarajan and senior technicians Tina Vo and Michael Socolich, who worked together to build the genes for the hybrid proteins.
The research was funded by DARPA.
For more information, visit: www.psu.edu
- 1. Synonymous with radioactivity. The intensity of a radioactive source illustrated as the number of atoms disintegrating in unit time, or as the number of scintillations or other effects observed per unit time. Activity is frequently expressed in curies, one unit being equal to 3.7 x 10-10 disintegrations per second. 2. In a reacting system, the evident effective concentration of a body of matter.
- Electromagnetic radiation detectable by the eye, ranging in wavelength from about 400 to 750 nm. In photonic applications light can be considered to cover the nonvisible portion of the spectrum which includes the ultraviolet and the infrared.
- The technology of generating and harnessing light and other forms of radiant energy whose quantum unit is the photon. The science includes light emission, transmission, deflection, amplification and detection by optical components and instruments, lasers and other light sources, fiber optics, electro-optical instrumentation, related hardware and electronics, and sophisticated systems. The range of applications of photonics extends from energy generation to detection to communications and...
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