"At those size scales, everything is dominated by friction," said Lipman, comparing the environment of a protein molecule in water to a human body in molasses. Friction between the molecule and its liquid environment is an issue, as well as the "dry" friction that is independent of the surrounding solvent.
Internal friction slows down the folding process by reducing the rate at which the amino acid chain explores different configurations that may lead to the transition state. The longer it takes to find its native state its final form the higher the likelihood it could get stuck in an unfolded state.
"When it is unfolded, it is more vulnerable to being trapped in a misfolded state, or to aggregation with other unfolded protein molecules," said Lipman. Aggregation of misfolded proteins is thought to be a contributor to many types of diseases, such as the amyloid plaques that are associated with Alzheimer's disease. Alternatively, the unfolded and not usable protein could be broken back up into its component amino acids by the cell.
While there is no confirmed link between internal friction and aggregation, or any pattern of friction for one protein that affects others in the same way, Lipman and his colleagues are getting closer to understanding the degree to which internal friction affects the protein folding process.
"These measurements show that under realistic conditions, internal friction plays a significant role in the dynamics of the unfolded state. If a model of the protein folding process doesn't account for this, it will need to be reconsidered," he said.
|Contact: Sonia Fernandez|
University of California - Santa Barbara