To say our genes are resourceful is a gross understatement. Through ingenious combinations of a paltry 20 amino acids, the basic building blocks of life, genes engineer all of the tissues and organs that are the marvel of our working bodies.
Now scientists are adding to the parsimonious genetic repertoire to good effect: With careful targeting using genetic engineering, so-called unnatural amino acids can effectively tag proteins that scientists want to study, because, like a lighthouse beacon in a soupy fog, they stand out from the ones the body already produces.
In work published last month in Nature Chemical Biology, new research at The Rockefeller University reveals a method that could theoretically be adapted to place a fluorescent probe at any position in any protein in a mammalian cell. The new technology could enable single-molecule fluorescent studies in live cells, says Thomas P. Sakmar, head of the Laboratory of Molecular Biology and Biochemistry. "It's a new tool to study membrane protein dynamics that should be of general use. We're building technologies to move the science forward."
Sakmar, research associate Thomas Huber and postdoctoral associate Shixin Ye, working with a colleague in Germany, Reiner Vogel, combined a variety of genetic engineering techniques to introduce an amino acid, azidoF, a relative of phenylalanine, into three points on rhodopsin, the light-sensitive cell receptor that is crucial to vision. The three-nitrogen-atom azido is an especially good probe for three reasons: In contrast to other tags, azido does not exist naturally in mammals, which makes it easier to "see;" it is small enough to not interfere with a protein's normal functioning; and it has chemical properties that make it a good handle on which to hang other molecules, like fluorescent probes, says Huber.