The protein go-slow: Giving NMR access

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  • Published: Oct 15, 2019
  • Author: David Bradley
  • Channels: NMR Knowledge Base
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Scientists have not been able to see proteins move  at speeds slower than a nanosecond. That changed with a discovery by a team at The Ohio State University. Image courtesy Wikimedia Commons.

A new approach to protein nuclear magnetic resonance (NMR) spectroscopy could open up study of even slow-moving biological macromolecules. NMR spectroscopy has emerged as a very useful tool for studying proteins, especially membrane bound proteins and others that are inaccessible to crystallographic techniques. However, protein dynamics on the nanosecond to microsecond timescale are usually off-limits even to NMR. Researchers at Ohio State University have now used nanoparticles to access NMR spin relaxation for slow-moving proteins.

“We know very little about what proteins do on timescales into the microseconds," explains Rafael Brüschweiler. "Traditional experiments provide very little information, because the way we test proteins now loses sensitivity at those speeds - there is a "bricked up" window, depending on how fast a protein is moving, at which we cannot see what the protein is doing and how it is behaving,” he adds. “Our goal here was to open up this window. To come up with a tool to measure how proteins function on these timescales that we have not been able to watch before.”

Unbricking the window

Brüschweiler's team has been searching for new ways to study proteins for many years. NMR spectroscopy is their tool of choice. “On the slower NMR timescale, the information about those proteins is just washed away – it is there, but our tools could not see it,” Brüschweiler said. “We thought there was slower motion present, but it was not observable.”

Now, the team has used silica nanoparticles as support agents in the NMR tube. Proteins bond to silica making even their slow movements visible to the technique. The discovery will protein scientists look in greater detail at protein behaviour and perhaps answer questions about how proteins interact with other proteins or drug molecules. “That’s the type of information we need in order to understand the function of proteins," Brüschweiler adds.

...and relax

Brüschweiler describes his first attempts to solve this problem a quarter of a century ago as “rigorous and nice…but ultimately a spectacular failure.” He had almost accepted that observing proteins with NMR on a slower timescale than the nanosecond might not be possible. However, work on nanoparticles in biological fluids unbricked that window for the team. Fundamentally, the team explains that they have "demonstrated how transverse spin relaxation becomes exquisitely sensitive to these motions at atomic resolution when studying proteins in the presence of nanoparticles."

Related Links

Sci Adv 2019, online: "Functional protein dynamics on uncharted time scales detected by nanoparticle-assisted NMR spin relaxation"

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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