Unfolding Acrobatic Proteins

Thursday, November 19 2009

Written by Ken Kingery

MOSCOW, Idaho – Scientists will soon attempt to unfold the secrets of a class of proteins that change their shape more often than a Ringling Brothers’ contortionist.

Backed by a $360,000 grant from the National Institutes of Health, computational biophysicists from the University of Idaho will join hands-on researchers from the University of South Florida in a project to understand the basic structures of proteins that change shape.

“Because this class of proteins changes shape, they can perform many different functions in the body,” said Marty Ytreberg, professor of computational and theoretical molecular biophysics at the University of Idaho. “So it is very important to understand how they work.”

However, gaining that understanding is easier said than done.

The class of proteins to which Ytreberg is referring is called intrinsically unstructured proteins, or IUPs. Scientists believe that up to 30 percent of the proteins in the human body exist in this class that constantly change shape and perform multiple functions. But because they’re constantly undergoing origami, it is very difficult for researchers to determine the different structures they take on, which is essential for understanding their functions in human health.

Much of the current research on IUPs focuses on what the proteins do rather than on determining their structures. Scientists put the proteins in a wide array of situations and see how they react; very few are researching the actual structures and mechanisms because it is intrinsically difficult to do.

There are two primary ways that scientists can determine a protein’s structure: x-ray crystallography and nuclear magnetic resonance (NMR). The former requires the crystallization of the protein, which forces it to stay in one shape, defeating the purpose of the study on those that change shape, such as IUPs. The latter observes a changing protein over a period of time rather than at a single point in time, creating a mess of data.

“You can’t make heads or tails of it,” said Ytreberg. “Because it is averaging the data over all of these different structures, it ends up just being a blur.”

But Ytreberg believes he may have found a way around this problem.

Over the next few months, Ytreberg will use computers to simulate millions – if not billions – of possible structures that the IUPs could take. His colleagues at the University of South Florida then will use NMR to collect data on the protein’s actual structure. Then the team will wade through it all to see which simulated structures fit best with the actual data.

“Basically, the idea is to take a simulated structure and suppose that it was the only structure the IUP could take,” said Ytreberg. “Then you see if that structure shows up at all in the experiment. If it does, you keep it. If it doesn’t, you throw it away. Then, you weigh it based on the strength of the match. In theory, the idea behind the project is pretty straight forward. But in practice, it’s going to be tricky.”
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About the University of Idaho
Founded in 1889, the University of Idaho is the state’s flagship higher-education institution and its principal graduate education and research university, bringing insight and innovation to the state, the nation and the world. University researchers attract nearly $100 million in research grants and contracts each year; the University of Idaho is the only institution in the state to earn the prestigious Carnegie Foundation classification for high research activity. The university’s student population includes first-generation college students and ethnically diverse scholars. Offering more than 130 degree options in 10 colleges, the university combines the strengths of a large university with the intimacy of small learning communities. For information, visit www.uidaho.edu.

About the University of Idaho
The University of Idaho helps students to succeed and become leaders. Its land-grant mission furthers innovative scholarly and creative research to grow Idaho's economy and serve a statewide community. From its main campus in Moscow, Idaho, to 70 research and academic locations statewide, U-Idaho emphasizes real-world application as part of its student experience. U-Idaho combines the strength of a large university with the intimacy of small learning communities. It is home to the Vandals. For information, visit www.uidaho.edu.