A group of researchers at Technical University of Munich and the Helmholtz Zentrum München (both Germany) have successfully uncovered the mechanism of interaction between small heat shock proteins and other proteins. The findings may help in the development of small heat shock proteins as a method for counteracting the characteristic clumping of proteins in neurodegenerative diseases such as Alzheimer’s.
Despite researchers being aware of the ability of small heat shock proteins to prevent badly folded proteins from clumping together, the precise role of small heat shock proteins was previously unknown. The new study, led by Bernd Reif (Technical University of Munich & Helmholtz Zentrum München), however has for the first time utilized solid-state nuclear magnetic resonance spectroscopy to precisely identify the alpha-B-crystallin sites that attach to beta-amyloid, the key protein aggregation in Alzheimer’s disease.
It was determined that the small heat shock protein utilizes a specific non-polar beta-sheet structure pile in its center for interactions with the beta-amyloid, allowing it to access the aggregation process in two locations at the same time. This involves attachment to individual dissolved beta-amyloids and prevention of the formation of fibrails, as well as ‘sealing’existing fibrils to ensure that no further amyloids can accumulate.
The research team now aim to analyze the N-terminal region of the alpha-B-crystallin even more closely, as unlike beta-amyloid it is able to bind protein types that clump in an unordered manner.