Unfolding of protein 'filmed' in atomic resolution
12 Feb 2013
Scientists have filmed the complex process of protein folding for the first time.
Scientists have, for the first time, rendered visible - at atomic resolution - how a protein progressively loses its shape.
In doing so, the researchers had pinned their hopes on low temperatures.
“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 group.
The research was undertaken by the Max Planck Institute for Biophysical Chemistry (MPIbpc) and the German Center for Neurodegenerative Diseases (DZNE) in Göttingen, together with the Polish Academy of Sciences in Warsaw and at the University of Warsaw,
Zweckstetter’s team chose a key protein for toxin production in Enterococcus faecalis, a pathogen frequently encountered in hospitals where it particularly jeopardizes patients with a weak immune system.
Some time ago, researchers working with Stefan Becker at the MPIbpc succeeded in elucidating its structure, which shows: Its three-dimensional shape makes CylR2 a particular promising candidate for the scientists’ approach.
Stefan Becker’s group undertook the first step: to prepare a sufficient quantity of the protein in the laboratory. Subsequently, the two chemists cooled the protein successively from 25°C to -16°C and examined its intermediate forms with NMR spectroscopy.
They achieved what they had hoped for: Their “film clip” shows at atomic resolution how the protein gradually unfolds. The structural biologist Markus Zweckstetter describes exactly what happens in this process:
“We clearly see how the CylR2 protein ultimately splits into its two subunits. The individual subunit is initially relatively stable. With further cooling, the protein continues to unfold and at -16 °C it is extremely instable and dynamic. This instable protein form provides the seed for folding and can also be the “trigger” for misfolding.”
The scientist’s findings may help to gain deeper insights into how proteins assume their spatial structure and why intermediate forms of certain proteins misfold in the event of illness.
