Researchers at the University of Washington have developed a new technique for observing large proteins that gives scientists the most detailed picture yet of the biological workhorses in action and promises to shed light on a wide range of issues, including the biocompatibility of medical implants, blood-clotting processes and how cancer spreads.
"To a large extent, a protein's structure determines its function," said Viola Vogel, associate professor of bioengineering and director of the UW's Center for Nanotechnology. "But, for very large proteins, the precise correlation is poorly defined. Now we have a very efficient way of tracking changes in structure so we can see how it relates to what these large proteins do."
Details of the new application of the technique, known as fluorescence resonance energy transfer, appear in the latest issue of Proceedings of the National Academy of Sciences.
Large proteins are made up of numerous amino acids, strung together in sequence like a strand of pearls. The structure of the protein changes depending on whether those pearls are tightly packed or whether the strand is extended. Along the strand are reactive sites that can bind with other molecules to perform various functions.
Those sites can be buried if the protein folds upon itself, which means they wouldn't be available to bind. Thus, changes in a protein's structure - whether it's compactly folded, unfolded or at some point in between - can change its performance.
Vogel and doctoral students Gretchen Baneyx and Loren Baugh did their initial experiments using fibronectin, a large protein that acts as a sort of super glue to hold cells together. The protein weaves itself into "sticky" attachment sites on cell surfaces and forms thread-like fibrils to connect the cells to one another. Fibronectin plays important roles in embryo development, wound healing and other vital biological functions.