Biochemists Lila Gierasch and Beena Krishnan at the University of Massachusetts Amherst have found a way to slip a fluorescent marker into one of a cell's molecular machines so it lights up when it has formed the proper shape to carry out the cell's "work orders." The new technique should allow labeling of correctly folded proteins in a living cell or similar natural environment, to study the origins of protein-misfolding diseases such as cystic fibrosis, Alzheimer's, and Parkinson's.
Proteins carry out thousands of normal cell operations by folding themselves into different 3D shapes matched to a single job. It's believed that misfolding occurs regularly and when a cell detects mistakes, it just recycles protein parts and uses them again. However, proteins may aggregate or clump with devastating results. The biochemists snipped a segment of naturally occurring protein and replaced it with what they dub a "cross-strand tetra-Cys motif." When the two parts of the motif settle near each other when properly folded, the dye binds and gives off light, allowing it to be seen against the background of cellular complexity.