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Penn scientists pioneer new method for watching proteins fold
Date:12/23/2011

nd laser acts as the camera, following the motions of the protein's constituent amino acids.

"The protein is made of different groups of atoms, and the different groups can be thought of as springs," Gai said. "Each spring has a different frequency with which it moves back and forth, which is based on the mass of the atom on either end. If the mass is bigger, the spring oscillates slower. Our 'camera' can detect the speed of that motion and we can relate it to the atoms it is made of and how that segment of the protein chain moves."

Even in a simple protein like Trp-cage, however, there are many identical bonds, and the researchers need to be able to distinguish one from another in order to see which of them are moving while the protein folds. One strategy they used to get around this problem was to employ the molecular equivalent of a tracking device.

"We use an amino acid with a carbon isotope marker," Culik said. "If it's incorporated into the protein correctly, we'll know where it is."

With a single carbon atom of the Trp-cage slightly heavier than the others, the research team can use its signature to infer the position of the other atoms as they fold. The researchers could then "tune" the frequency of their laser to match different parts of the protein, allowing them to isolate them in their analyses.

Similar isotopes could be inserted in more complicated molecules, allowing their folds to also be viewed with infrared spectroscopy.

"This technique enhances our structural resolution. It allows us to see which part is moving," Gai said. "That would allow us to see exactly how a protein is misfolding in a disease, for example."


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Contact: Evan Lerner
elerner@upenn.edu
215-573-6604
University of Pennsylvania
Source:Eurekalert

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