Protein “filmed” while unfolding at atomic resolution
When proteins get “out of shape”, the consequences can be fatal. They lose their function and in some cases form insoluble, toxic clumps that damage other cells and can cause severe diseases such as Alzheimer’s or Parkinson’s. Researchers at the Max Planck Institute for Biophysical Chemistry and the German Center for Neurodegenerative Diseases in Göttingen - in collaboration with Polish colleagues - have now “filmed” how a protein gradually unfolds for the first time. By combining low temperatures and NMR spectroscopy, the scientists visualized seven intermediate forms of the CylR2 protein while cooling it down from 25°C to - 16°C. Their results show that the most instable intermediate form plays a key role in protein folding. The scientists’ findings may contribute to a better understanding of how proteins adopt their structure and misfold during illness. (Nature Chemical Biology, 10. February 2013)“Snapshot” of the unfolding of the CylR2 protein from Enterococcus faecalis. If the protein is cooled from 25°C… [more] © Zweckstetter, Max Planck Institute for Biophysical Chemistry & German Center for Neurodegenerative Diseases
Whether Alzheimer’s, Parkinson’s or Huntington’s Chorea - all three diseases have one thing in common: They are caused by misfolded proteins that form insoluble clumps in the brains of affected patients and, finally, destroy their nerve cells. One of the most important questions in the biological sciences and medicine is thus: How do proteins - the tools of living cells - achieve or lose their three-dimensional structure. Because only if their amino acid chains are correctly folded, can proteins perform their tasks properly.
But what exactly happens when proteins fold or unfold was previously nearly impossible to investigate. With heat and pressure, proteins easily lose their shape - and thus their function. However, such methods are not suitable for directly observing their unfolding process. The intermediate forms that occur in the course of protein folding are much too transient.
With a novel approach, researchers have now succeeded in “filming” the complex process of protein folding for the first time.