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NMR advance brings proteins into the open

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Posted June 25, 2013
In this computer rendering a GroEL chaperone protein (larger) is about to capture an A-Beta protein (smaller). Credit: Nicolas Fawzi/Brown University

In this computer rendering a GroEL chaperone protein (larger) is about to capture an A-Beta protein (smaller). Credit: Nicolas Fawzi/Brown University

When working a cold case, smart investigators try something new. By taking a novel approach to nuclear magnetic resonance spectroscopy – a blending of four techniques – scientists have been able to resolve a key interaction between two proteins that could never be observed before. They report on their findings the week of June 24, 2013 in Proceedings of the National Academy of Sciences (PNAS).

The interaction the team became the first to describe is nearly universal across all of life. A protein machines called a chaperone takes hold of a disordered smaller protein to help it find its proper folded conformation. In this case, the team set up test-tube experiments where they hoped to watch the capsule-shaped bacterial chaperone GroEL capture a disordered amyloid beta; (A-beta) protein, a molecule that in humans is central in Alzheimer’s disease.

The two proteins are well studied, but the motions they go through when they first meet – when the open GroEL capsule captures its target – have been invisible to scientists. Electron microscopy and x-ray crystallography are only good for taking snapshots of easily frozen moments in time. NMR is capable of sensing the interactions and kinetics of protein handshakes as they occur, but in some cases any single technique can provide only hints and whispers of what’s going on.

Brown University biologist Nicolas Fawzi, who was a post-doc in the group of Marius Clore’s at the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) within the National Institutes of Health (NIH), worked with co-authors and NIDDK researchers David Libich, Jinfa Yang and Marius Clore to piece together the story of the proteins by combining four different NMR techniques. They figured out what each one could tell them about the interaction and built the case presented inPNAS.

Read more at: Phys.org

 

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