Biochemists have made a fundamental discovery about protein structure that sheds new light on how proteins fold, one of the most basic processes of life. Even the process of thinking involves proteins at the end of one neuron passing a message to different proteins on the next neuron.
Scientists previously thought is was impossible to characterize these changes, in part because the transitions are so incredibly small and fleeting. Proteins convert from one observable shape to another in less than one trillionth of a second, and in molecules that are less than one millionth of an inch in size. These changes have been simulated by computers, but no one had ever observed how they happen.
“Actual evidence of these transitions was hiding in plain sight all this time,” said Andrew Brereton, an OSU doctoral student and lead author on this study. “We just didn’t know what to look for, and didn’t understand how significant it was.”
X-ray crystallography has been able to capture images of proteins in their more stable shapes. But the changes in shape needed for those transitions are fleeting and involve distortions in the molecules that are extreme and difficult to predict.
What the OSU researchers discovered is that these stable shapes actually contained some parts that were trapped in the act of changing shape, conceptually similar to finding mosquitos trapped in amber.
“We discovered that some proteins were holding single building blocks in shapes that were supposed to be impossible to find in a stable form,” said Andrew Karplus, the corresponding author on the study and a distinguished professor of biochemistry and biophysics in the OSU College of Science.
“Apparently about one building block out of every 6,000 gets trapped in a highly unlikely shape that is like a single frame in a movie,” Karplus said. “The set of these trapped residues taken together have basically allowed us to make a movie that shows how these special protein shape changes occur. And what this movie shows has real differences from what the computer simulations have predicted.”
As with most fundamental discoveries, the researchers said, the full value of the findings may take years or decades to play out.