Studies of small protein fragments are not representative of full amyloid fibrils

The formation of amyloid fibrils, a protein aggregate, is connected to a number of diseases, such as Alzheimer’s, Parkinson’s and type-II diabetes. However, since it is difficult to fully explore the formation of these fibrils due to their complexity, many investigations study the behavior of smaller fragments of the full protein instead. To determine how representative this approach is of the larger protein structure, Suman Samantray and David Cheung evaluated the behaviors of amyloids at different lengths and in different environments.

“There are many interfaces in the body that proteins can adsorb onto, principally membranes, so understanding aggregation on interfaces can give insight into the fibril formation in the body,” said Cheung.

Samantray and Cheung used molecular dynamics simulations to characterize the behavior of a single protein molecule at the air-water interface as well as in a bulk fluid. They examined the structures formed using cluster analysis and determined the probability of each potential conformation.

They found that both longer and shorter fragments are more likely to form ordered structures and more prone to aggregation at air-water interfaces than in bulk fluid solutions. Fragments closer in size to the full protein see a more dramatic difference, forming helical structures very different from those formed in bulk fluids. This, along with increased protein concentrations at interfaces, can lead to a surge in fibril formation. They plan to further the study to include more complex interfaces and fibrils to gain a better insight into fibril formation in various biological environments.

“While the full-length protein is involved in biological processes, the smaller fragments are often used as proxies for this,” Cheung said. “This suggests that care should be taken when doing this.”

Source: “Effect of the air-water interface on the conformation of amyloid beta,” by Suman Samantray and David L. Cheung, Biointerphases (2020). The article can be accessed at https://doi.org/10.1116/6.0000620 .

This paper is part of the Molecular Scale Modeling of Biological Molecules at Interfaces Collection. Learn more here .