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. Scientists at the Max Planck Institute for Biophysical Chemistry (MPIbpc) and the German Center for Neurodegenerative Diseases (DZNE) in Göttingen, together with their colleagues at the Polish Academy of Sciences in Warsaw and at the University of Warsaw, have rendered visible -- at atomic resolution -- how a protein progressively "loses its shape." In doing so, the researchers had pinned their hopes on low temperatures. "If a protein is slowly cooled down, its intermediate forms accumulate in larger quantities than in commonly used denaturation methods, such as heat, pressure, or urea. We hoped that these quantities would be sufficient to examine the intermediate forms with nuclear magnetic resonance (NMR) spectroscopy," said Markus Zweckstetter, head of the research groups "Protein Structure Determination using MNR" at the MPIbpc and "Structural Biology in Dementia" at the DZNE in Göttingen.
No comments:
Post a Comment