Researchers have discovered how the blood plasma protein fetuin-B binds to the enzyme meprin β and used a computer model to visualize their findings. These results could lead to the development of new drugs to treat serious diseases such as Alzheimer's and cancer.
Meprin β releases proteins from cell membranes, thus controlling important physiological functions in the human body. However, a dysregulation of this process can trigger the development of Alzheimer's and cancer. Meprin β is regulated by fetuin-B binding to the enzyme when required, thereby preventing the release of other proteins. Presenting their findings in the journal "Proceedings of the National Academy of Sciences", the researchers are now the first to describe this binding in detail.
The team produced both meprin β and fetuin-B in insect cells and then allowed them to react with one other in a test tube. By means of measurement of enzyme kinetics and biophysical analyses, the researchers determined that this reaction resulted in an exceptionally stable, high-molecular-mass complex.
They subsequently managed to crystallize the complex and determine its three-dimensional structure using X-ray crystallography. This involved X-rays being fired at the protein crystals, which allowed the atomic structure of the crystals to be calculated from the diffraction of the X-rays. A computer model of the structure was then generated.
"Thanks to the model, we can now see exactly how meprin β and fetuin-B bind together," said the senior author. "This research represents an excellent starting point for gaining a better understanding of diseases such as Alzheimer's and for developing the drugs to combat them."
Meprin β is already known to be involved in the formation of so-called beta-amyloid plaques, which are a characteristic feature of the condition. Moreover, people with Alzheimer's disease have relatively little fetuin-B in their blood, which in turn may lead to a lack of regulation of meprin β. "If it is possible to develop a drug that binds to the enzyme and inhibits it in a similar way to fetuin-B, this could be a new way of treating Alzheimer's," concluded the author.
https://www.uni-mainz.de/presse/aktuell/13477_ENG_HTML.php
https://www.pnas.org/content/118/14/e2023839118
Inhibition of meprin-beta enzyme linked to the development of Alzheimer's disease
- 1,245 views
- Added
Edited
Latest News
Metabolic rewiring promotes…
By newseditor
Posted 18 Apr
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Other Top Stories
Autosomal dominant Alzheimer's disease and mechanisms of disease pr…
Read more
Genetic and biochemical determinants of brain calcification
Read more
The same protein controls brain size and infertility
Read more
Age-related cognitive decline tied to immune-system molecule
Read more
Mechanism of microglial self-renewal in the brain
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar