Proteins like the so-called heat shock protein Hsp90 play an important role in almost all processes within human cells. They help other proteins fold into their three-dimensional structure or return damaged proteins back into their proper shape.
Recently, there has been increasing evidence indicating that the heat shock protein HSP90 may also be involved in the folding processes of the tau protein. Deposits of tau proteins in brain cells are typical for Alzheimer's disease and are held responsible for decaying nerve cells.
Hsp90 and Tau: how are they linked?
The protein complex consisting of Hsp90 and Tau is very dynamic. How Hsp90 and tau protein interact and how Hsp90 influences the aggregation of tau proteins with one another has now been resolved by an international team headed by Dr. Tobias Madl, leader of the Emmy-Noether Group Structural Biology of Signal Transduction at the Institute of Structural Biology at the Helmholtz Zentrum München and leader of the BioSysNet Working Group and TUM Junior Fellow at the Technische Universität München as well as Prof. Stefan Rüdiger from the Dutch University of Utrecht.
For their studies they used a combination of very different techniques like magnetic resonance spectroscopy, small-angle X-ray scattering and computer modeling, to determine structure and dynamics of the interactions between the two biomolecules. While dissolved tau proteins look more like long, stretched chains, HSP90 binds predominantly proteins that have already been prefolded. This contradiction has now been resolved: For Hsp90 the tau protein looks like a prefolded larger protein.
Influencing structural formation
"Deposits of tau proteins are associated with Alzheimer's disease. We have discovered the protein regions in which the proteins interact. This is a novel and important starting point for influencing structural formation and for developing future therapies for Alzheimer's disease," says Madl.
In addition to Alzheimer's disease, further neurodegenerative diseases are caused by protein aggregation. Folding proteins also play a role in the development of cancer and cystic fibrosis. These scientific insights thus provide an important basis for better understanding the disease mechanisms.
German Research Foundation