Proteins are strung together from amino acids attached in long chains, one after the other. But for most proteins, this is just the beginning – next they must fold. “Folding” is the general term for the way that a protein strand twists, coils, winds, pleats and creases into an intricate three-dimensional structure. Only then can it go to work.
The sequence of amino acids is what determines the final shape of the protein: Molecules assembled on the same plan will end up in the exact same configuration. The funny thing is, they don’t all go through the same set of steps to arrive at their final structure. Some of them, apparently, take shortcuts. It’s as if you could skip a few steps in the origami instructions and still end up with a perfect paper crane in the end.
To observe and compare how individual protein strands fold, the Weizmann Institute’s Prof. Gilad Haran and his team had to invent some new techniques, including fluorescent microscopy methods and data analysis that enabled them to collate thousands of individual events into a timeline of protein folding.
The team identified six different intermediate configurations for the protein they studied. Sometimes the strands went through all of them; other times, they took an easier, shorter route to their final form.
Why would a molecule go through extra contortions to get to the same state? The findings contain a clue: The process became longer and more tortuous in the presence of some external factors such as heat or higher concentrations of certain chemicals in the protein’s environment.
Like much good research, this study raises more questions than it answers: Is this a general rule that holds for different types of proteins? What advantages do the different routes to protein structure confer? How this might tie into such disorders as Alzheimer’s disease, in which badly-folded proteins form plaques in brain tissue?