New research divines structure for class of proteins

Sep 21, 2010 By Richard Lewis
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.

(PhysOrg.com) -- 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, "We don't know much about them," said Wolfgang Peti, associate professor of medical science and chemistry. "No one really worried about them."

Now, Peti, joined by researchers at the University of Toronto and at Brookhaven National Laboratory in New York, has discovered the structure of three IDPs — spinophilin, I-2, and DARPP-32. Besides getting a handle on each protein's shape, the scientists present 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 phosphatase 1, known as "folding upon binding." The findings are reported in the journal Structure.

Determining the IDPs' shape is important, Peti explained, because it 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.

"What we see is some don't have to change much, and some have to change a lot," Peti, a corresponding author on the paper, said. "That may be a signature how that (binding) interaction happens."

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 to create ensemble calculations for the protein in its free and PP1-bound form. They confirmed I-2's binding interaction with PP1 (known as the PP1:I-2 complex) with the help of small-angle x-ray scattering measurements at the , located at the Brookhaven lab.

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.

"It's analogous to putting a sack cloth over a person," Peti explained. "You can't see the details, but you can get the overall shape. This is really a new way to create a model for highly dynamic complexes."

Julie Forman-Kay, a senior scientist at the Hospital for Sick Children in Toronto and a biochemistry professor at the University of Toronto, is a co-corresponding author on the paper. Other authors include Barbara Dancheck and Michael Ragusa, Brown graduate students; Joseph Marsh, a graduate student at the University of Toronto; and Marc Allaire, a biophysicist at the Brookhaven lab.

Explore further: 'Hairclip' protein mechanism explained

More information: J.A. Marsh, et al, "Structural Diversity in Free and Bound States of Intrinsically Disordered Protein Phosphatase 1 Regulators," Structure 18(9) 1094 (2010).

Related Stories

Research divines structure for class of proteins

Sep 08, 2010

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 ...

Work with fungus uncovering keys to DNA methylation

Dec 15, 2008

Researchers in a University of Oregon lab have shed more light on the mechanism that regulates DNA methylation, a fundamental biological process in which a methyl group is attached to DNA, the genetic material in cells of ...

Recommended for you

'Hairclip' protein mechanism explained

11 hours ago

Research led by the Teichmann group on the Wellcome Genome Campus has identified a fundamental mechanism for controlling protein function. Published in the journal Science, the discovery has wide-ranging implications for bi ...

Discovery in the fight against antibiotic-resistant bacteria

13 hours ago

For four years, researchers at Universite catholique de Louvain have been trying to find out how bacteria can withstand antibiotics, so as to be able to attack them more effectively. These researchers now understand how one ...

Stem cells born out of indecision

13 hours ago

Scientists at the University of Copenhagen have gained new insight into embryonic stem cells and how blocking their ability to make choices explains why they stay as stem cells in culture. The results have just been published ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.