Most proteins are shapely, but about one-third of them lack a definitive form, at least that scientists can readily observe. These intrinsically disordered proteins (IDPs) perform a host of important biological functions, from muscle contraction to other neuronal actions. Yet despite their importance, scientists don’t know much about them.
Now, researchers at Brown University, the University of Toronto, and Brookhaven National Laboratory have discovered the structure of three IDPs — spinophilin, I-2, and DARPP-32. Besides getting a handle on each protein’s shape, the scientists presented for the first time how these IDPs exist on their own (referred to as “free form”) and what shape they assume when they latch on to protein phosphatase 1, known as “folding upon binding.”
Determining the IDPs’ shape gives molecular biologists insight into what happens when IDPs fold and regulate proteins, such as PP1, which must occur for biological instructions to be passed along.
For two years, the researchers used a variety of techniques to ascertain each IDP’s structure. With I-2, which instructs cells to divide, they used nuclear magnetic resonance spectroscopy to create ensemble calculations for the protein in its free and PP1-bound form. They confirmed I-2’s binding interaction with PP1 with the help of small-angle x-ray scattering measurements at NSLS.
The researchers did the same thing to determine the structure of spinophilin and DARPP-32 in their free-form state and to gain insights into their shapes when they bind with PP1.
— Richard Lewis, Brown University
J.A. Marsh, B. Dancheck, M.J. Ragusa, M. Allaire, J.D. Forman-Kay, W. Peti, "Structural Diversity in Free and Bound States of Intrinsically Disordered Protein Phosphatase 1 Regulators," Structure, 18(9), 1094, (2010).
Left: Researchers used a variety of experimental, mathematical and observational
techniques to ascertain how I-2, one of a class of poorly understood proteins known
as intrinsically disordered proteins, binds with the regulator protein phosphatase 1.
Right: Lead researcher Wolfgang Peti, associate professor of medical science and chemistry at Brown University