Featured Research

from universities, journals, and other organizations

Key enzyme discovered to be master regulator in protein-protein reactions

Date:
March 29, 2010
Source:
Brown University
Summary:
New research explains how a key enzyme, PP1, functions in protein-protein interactions. Researchers have described how PP1 "chooses" proteins. The finding is important, because erroneous PP1 regulation can cause numerous diseases, including cancer, diabetes and Parkinson's.

The Master Regulator Research led by Wolfgang Peti of Brown University shows how a phosphatase called PP1 becomes more selective in protein-protein interactions. In the illustration, the phosphate spinophilin binds to one of PP1's three available binding sites, reducing the number of available substrates for other proteins.
Credit: Wolfgang Peti, Brown University

Protein phosphorylation is a process by which proteins are flipped from one activation state to another. It is a crucial function for most living beings, since phosphorylation controls nearly every cellular process, including metabolism, gene transcription, cell-cycle progression, cytoskeletal rearrangement and cell movement.

Related Articles


Due to its importance in biology, scientists have wanted to learn more about protein phosphorylation and how proteins know when and how to become phosphorylated or dephosphorylated. Think of it like choosing the right dance partner who knows your moves so intimately that the choreography is seamless. Biologists have learned that interactions by kinases (enzymes that add a phosphate to a protein) are highly regulated. Each of the 428 human serine/threonine kinases interact only with certain substrate proteins, and they pick their "partners" unfailingly. But for the reverse reaction, called dephosphorylation (removing a phosphate from a protein), only about 40 phosphatases are available to interact with all substrate proteins. In fact, just one of them, protein phosphatase 1 (PP1), is believed to be responsible for up to 65 percent of dephosphorylation reactions.

The question then is how PP1, a generalist, knows which substrate proteins to interact with. New research by Wolfgang Peti, the Manning Assistant Professor of Medical Science and assistant professor of chemistry, reported in a paper published online in Nature Structural & Molecular Biology, helps to answer that question. Peti and colleagues at Brown and Yale University have discovered that PP1 "chooses" proteins in dephosphorylation reactions based on which of its binding sites is available for the interaction to occur. The finding is important, because erroneous PP1 regulation can cause numerous diseases, including cancer (chromatin remodeling), diabetes (glycogen) and Parkinson's (LTP).

"There are thousands of (peer-reviewed) papers out there, but nobody understood how PP1 is regulated," said Peti. "It is in fact a master regulator. We have identified now how it works."

To obtain their results, the team showed for the first time how PP1 is bound to a regulator protein, spinophilin. Using nuclear magnetic resonance spectroscopy and X-ray crystallography, the researchers examined the spinophilin-PP1 complex's structure. The scientists saw that spinophilin had attached itself to one of three substrate binding sites on PP1, called the C-terminal substrate binding groove. Examined at the atomic scale, it appears as if spinophilin is a many-tentacled beast that has woven itself into the C-terminal substrate binding groove, effectively blocking any substrate requiring this groove from interacting with PP1.

That leaves only two other binding sites, the acidic and hydrophobic substrate binding grooves. "Any substrate that needs the C-terminal is out of the game," Peti said.

By narrowing the binding sites from three to two, PP1 is in effect becoming more selective, Peti noted. "What that means is PP1 is equally tightly controlled as kinases are," he said.

"Now we know how PP1 is regulated," Peti added. "What simply happens is we don't create more enzymes. We create more protein complexes (holoenzymes) that increase the specificity of PP1."

Rebecca Page, assistant professor in the Department of Molecular Biology, Cell Biology and Biochemistry at Brown, is a contributing author on the paper. In addition, Brown graduate students Barbara Dancheck, David Critton and Michael Ragusa assisted in the research. Angus Nairn, professor at psychiatry at Yale, contributed to the paper.

The research was funded by the National Institutes of Health and a National Science Foundation Graduate Research Fellowship.


Story Source:

The above story is based on materials provided by Brown University. Note: Materials may be edited for content and length.


Cite This Page:

Brown University. "Key enzyme discovered to be master regulator in protein-protein reactions." ScienceDaily. ScienceDaily, 29 March 2010. <www.sciencedaily.com/releases/2010/03/100324121015.htm>.
Brown University. (2010, March 29). Key enzyme discovered to be master regulator in protein-protein reactions. ScienceDaily. Retrieved December 20, 2014 from www.sciencedaily.com/releases/2010/03/100324121015.htm
Brown University. "Key enzyme discovered to be master regulator in protein-protein reactions." ScienceDaily. www.sciencedaily.com/releases/2010/03/100324121015.htm (accessed December 20, 2014).

Share This


More From ScienceDaily



More Plants & Animals News

Saturday, December 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Monarch Butterflies Descend Upon Mexican Forest During Annual Migration

Monarch Butterflies Descend Upon Mexican Forest During Annual Migration

Reuters - Light News Video Online (Dec. 19, 2014) Millions of monarch butterflies begin to descend onto Mexico as part of their annual migration south. Rough Cut (no reporter narration) Video provided by Reuters
Powered by NewsLook.com
The Best Protein-Filled Foods to Energize You for the New Year

The Best Protein-Filled Foods to Energize You for the New Year

Buzz60 (Dec. 19, 2014) The new year is coming and nothing will energize you more for 2015 than protein-filled foods. Fitness and nutrition expert John Basedow (@JohnBasedow) gives his favorite high protein foods that will help you build muscle, lose fat and have endless energy. Video provided by Buzz60
Powered by NewsLook.com
Birds Might Be Better Meteorologists Than Us

Birds Might Be Better Meteorologists Than Us

Newsy (Dec. 19, 2014) A new study suggests a certain type of bird was able to sense a tornado outbreak that moved through the U.S. a day before it hit. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Plants & Animals

Earth & Climate

Fossils & Ruins

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins