Proteins are the building blocks of life. They are present in every cell in the human body and perform essential structural and metabolic functions. Defects in proteins can also lead to disease. That’s why detailed studies on proteins, their structure and the complex interactions between them are so important. Conventional structural analysis is often performed on single proteins. Most proteins, however, form a network of interactions and many exist as components of larger complexes. Producing and analyzing these molecular machines in sufficient quantity and quality often poses huge difficulties.
ProteoPlex technologies help researchers gain a better understanding of the structure and function of macromolecular complexes. The MacroDSF instrument makes it possible to perform structural analyses which, until now, due to the difficultly of obtaining sufficiently high-quality samples, were simply not feasible. To analyze the structure of molecular machines using x-ray crystallography and cryo-electron microscopy, they first have to be purified and often crystallized. Unlike small molecules such as sugar, macromolecular complexes, featuring irregular three-dimensional structures, do not form crystals in their natural environment. They can only be crystallized under very specific conditions and crystallization depends on a range of factors. ProteoPlex MacroDSF technology helps in determining the ideal concentrations, buffers and additives to optimize crystallization and stabilization of these proteins. The result is that it is finally possible to research the 3D structure of these macromolecular machines.
In their research, co-founders Holger Stark and Ashwin Chari used a range of innovative technologies to determine the structure of and to produce extremely high-quality proteasomes. Proteasomes are cellular waste disposal units, which recycle defective proteins, and proteins that are no longer required. Because cancer cells grow faster than most of the other cells in our bodies, they also produce more waste, and are particularly dependent on proteasomes to avoid drowning in their own waste products. Proteasomes therefore represent a promising target for cancer drug development. The proteasomes marketed by ProteoPlex have ten times the specific activity of proteasomes produced using current state of the art methods, and could help the pharmaceutical industry develop better inhibitors, which kill cancer cells by blocking proteasome activity.
ProteoPlex technologies are based on work on structural analysis of biological macromolecules by Holger Stark and Ashwin Chari at the Max Planck Institute for Biophysical Chemistry in Göttingen. Their research has significantly expanded our understanding of the function of such molecules and the factors behind the stability of large molecular complexes. “With the help of our refinements to MacroDSF technology and a novel purification technique, it is now possible to produce very large protein complexes which are pure enough to enable biological structural analysis to deliver significant new insights”, says Jörg Wamser, Managing Director of ProteoPlex GmbH, founded in 2016. The technologies have been exclusively licensed to ProteoPlex by Max Planck Innovation, the technology transfer organization of the Max Planck Society.
“Structural biology is a relatively new field of research with huge potential. Research at the Max Planck Institute for Biophysical Chemistry in Göttingen is providing important insights into interactions between molecules and their mode of action. We are therefore very pleased that the experienced team at ProteoPlex will be driving this important field of research forward on a commercial basis, and have already launched their first product,” says Bernd Ctortecka, patent and license manager at Max Planck Innovation.
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