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.