Visualizing Unfolded Protein Movement Within the Cell

It has long been assumed that unfolded proteins are slower than their folded counterparts. The assumption is usually on the basis of the common knowledge that bulky is heavier than compact. To shed more light on this, Professor Martin Gruebele spearheaded research to enable the witnessing of the actual movements of these proteins in the cell.

The observation was done by using fluorescent microscope. The microscope was used alongside three-dimensional diffusion modelling. The, findings of this research were that the bulkiness of the unfolded protein is not the sole determinant of the speed with which it moves inside the cell. Chaperone molecules probably play a bigger role than size. The research also found that there are instances when too many proteins come unfolded. When this happens, there may not be enough chaperone molecules to bind with.

According to the research, when there are no chaperone molecules available, to move the unfolded proteins, the entire cell may fail due to its inability to fulfill its roles.

It is normal for chaperones to join with unfolded proteins and help them move easily to all parts of the cell. If there is a high ratio of unfolding proteins joining with unfolded cells. The unfolded cells are not able to move easily. They find themselves in a veritable traffic jam which slows them down. Movement of these proteins is also slowed down by the fact that they also bind with molecules that are not chaperone. This crowds them making it difficult for them to move. Binding with non-chaperone molecules also causes other problems for the cell that make it even more difficult for the cell to fulfill its roles. They also hasten the path to total failure of the cell.

The speed of these proteins, however, was not found to be constant in a manner that the exact effect of large amounts of chaperone binding could be determined. The proteins moved faster in at certain parts of the cell and then slow down at others in an apparently random manner.

While the findings of this research are fascinating, there is no way of knowing whether they apply on all types of proteins or they can also apply on proteins of other types. It could be that each type of protein is affected differently by unfolding. It is for this reason that Professor Gruebele and the team want to conduct another research. In this other research, they will establish whether all proteins react the same to unfolding and chaperones or not. It will be deeper and it will give more clarity on the question of unfolding proteins.

It could be that mammalian, yeast and warm cells provide different environments for the cells to operate in. this would mean that the responses are different for different types of cells. The type of response that unfolded proteins give may lead to diseases such as prion. The responses may also lead to certain neurodegenerative diseases. This means that this research could be seminal in future for curing or managing such protein misfolding diseases.

Citation: Guo M, Gelman H, Gruebele M (2014) Coupled Protein Diffusion and Folding in the Cell. PLoS ONE 9(12): e113040. doi:10.1371/journal.pone.0113040