Scientists already know that the enzyme Meprin-β is involved in the formation of so-called beta-amyloid plaques, which are characteristic of Alzheimer's disease. The team of researchers has now discovered how exactly a blood plasma protein called Fetuin-B binds to the Meprin-β enzyme.

Fetuin-B is the regulator of Meprin-β by binding to the enzyme when necessary, thereby preventing the release of other proteins. However, the misregulation of proteins by Meprin-β could also cause diseases such as Alzheimer's. It has been observed that Alzheimer's patients have relatively low levels of Fetuin-B in their blood, possibly leading to a lack of control of Meprin-β.

For their studies, the JGU scientists generated both Meprin-β and Fetuin-B in insect cells and allowed them to react with each other in a petri dish. Through enzyme kinetic measurements and biophysical analyses, they determined that this reaction had produced an extremely stable high-molecular complex. Their colleagues in Barcelona subsequently succeeded in crystallizing the complex and elucidating its three-dimensional structure by X-ray crystal structure analysis.

Their findings could contribute to the development of drugs against serious diseases such as Alzheimer's or cancer.

Original publication:
Eckhard, U., Körschgen, H., Wiegen, von, N., Stöcker, W. & Gomis-Rüth, F. X. (2021). The crystal structure of a 250-kDa heterotetrameric particle explains inhibition of sheddase meprin β by endogenous fetuin-B. Proc. Natl. Acad. Sci. U.S.A. 118. doi.org/10.1073/pnas.2023839118.

Source:
https://www.uni-mainz.de/presse/aktuell/13477_DEU_HTML.php