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Intrinsically disordered proteins: A conversation with Rohit Pappu
Date:9/20/2012

If you open any biology textbook to the section on proteins, you will learn that a protein is made up of a sequence of amino acids, that the sequence determines how the chain of amino acids folds into a compact structure, and that the folded protein's structure determines its function. In other words sequence encodes structure and function derives from structure.

But the textbooks may have to be rewritten. As Rohit Pappu and two colleagues explain in a perspective published Sept. 20 in Science, a large class of proteins doesn't adhere to the structure-function paradigm. Called intrinsically disordered proteins, these proteins fail fold either in whole or in part and yet they are functional.

We sat down recently with Pappu, PhD, professor of biomedical engineering and director of the Center for Biological Systems Engineering at Washington University in St. Louis to catch up on the latest science.

When did people realize some proteins violate the rules?

It's been about 20 years. The earliest clue was that some protein segments didn't show up in X-ray crystallography or NMR studies, the standard ways of studying protein structure.

By the 1990s people who studied how proteins interact with DNA had noticed the proteins often change shape when they interact with DNA. In the absence of DNA all the standard probes for protein structure reported back that the proteins were floppy, and yet when the protein formed a complex with DNA it had a well-defined three-dimensional structure.

How did you first come to hear about them?

By serendipity. When I was leaving Johns Hopkins University to come to Washington University in 2001 I had a meeting with Keith Dunker of the Indiana University Schools of Medicine and Informatics, one of the founding fathers of this field. It was pure chance. The meeting started awkwardly because Keith was wondering who I was and I had never heard of him. I was
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Contact: Diana Lutz
dlutz@wustl.edu
314-935-5272
Washington University in St. Louis
Source:Eurekalert

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