Navigation Links
A 'dimmer switch' for genes

A protein that was thought to simply turn genes on and off now looks to be more like a cellular "dimmer switch," researchers from Huntsman Cancer Institute at the University of Utah, report in the July 1, 2005, issue of the journal Science.

The scientists showed for the first time that when certain parts of a protein molecule are modified ?flexible, randomly structured regions believed to be only minor players in the protein world ?they become important in turning genes on and off, but in a way that resembles a dimmer switch rather than an on-off switch.

Genes carry the code that produces proteins to carry out almost all functions in a living organism. But some of these proteins also help control when and where genes do their jobs. The new study deals with how one such protein, named Ets-1, turns genes on or off.

Huntsman Cancer Institute scientists, led by Barbara Graves, Ph.D., professor and chair of the Department of Oncological Sciences at the University of Utah School of Medicine, and doctoral student Miles Pufall, studied Ets-1, a protein known as a transcription factor that helps read genetic information. This factor serves as a cell's librarian, helping find the right genetic instructions.

How much information the librarian provides, and how accurate that information is, must be tightly controlled. Without the right information, cells can't behave properly, and may, as in the case of cancer, grow out of control. The connection between factors such as Ets-1 and a number of cancers prompted the study of how it works.

One way proteins are controlled occurs after a cell creates a protein. Graves illustrates this process by comparing protein structure with beads on a string. "After the protein is made, it can acquire what we call post-translational modifications, which are like decorations on a beaded necklace. In this analogy, one person creates a necklace using similar beads and then a committee comes along and decorates i t, putting a gold star here and a diamond there. These modifications give the protein different properties."

The "decorations" that were studied were phosphate molecules, which previously had been shown to build up on proteins until a certain number accumulated. The result, according to the study, has been described in the past as a sharp on-off switch of protein activity.

"What we found was that each time we added a phosphate to a particular unstructured region of Ets-1, there was an effect on the protein's ability to bind to a gene. Binding was weakened, but it was a gradual weakening. That isn't typical," Graves says. "Instead of acting like an on-off switch, it behaved the way a dimmer switch does to regulate lighting in a gradual manner."

In studying how this fine-tuning worked, they also discovered that conventional wisdom failed to fully describe how proteins function. It was known that proteins have regions with parts that are fixed in space, with a definite structure, and parts that are randomly positioned in space, like spaghetti strands. It was thought that the structured regions did most of the work, while the unstructured regions served only minor roles, such as tethering parts together.

"Scientists understand how a molecule works in part because we understand the shape or structure," Graves explains. "But what we discovered takes us beyond knowing the structure. Our data were about features that are not fixed in space, but that are flexible and changing."

The team used a nuclear magnetic resonance, or NMR, which allows scientists to observe how the atoms of a molecule behave inside a magnetic field. The Graves team found that unstructured regions of the Ets-1 protein were affecting the structured regions in the work of controlling genes. "In fact," Graves reports, "the region's unstructured nature appears to be an essential requirement." NMR showed that phosphate addition to this unstructured region caused a grad ual decline in DNA binding, gradually turning a gene off.

"One thing we didn't get was why Ets-1 worked differently before and after phosphorylation [the addition of phosphate]," says Pufall, "because as far as we could tell, the overall shape of the molecule didn't change."

"A protein molecule is not like a rock. It's more like Jell-O: it has structure, it has shape, but it jiggles," explains Graves. "We didn't discover jiggling, but we were able to determine that the amount of internal motion within a protein corresponds to the ability of a protein to do its work." Phosphorylation was found to decrease the internal motion of Ets-1, reducing its activity.

According to Pufall, "Ets-1 provides a remarkable illustration of how elegantly proteins are put together ?forming a distinct shape, but with the versatility to respond to the changing needs of the cell, however subtle."

The findings have long-term implications for the study of all proteins, because, according to Graves, any protein has the potential to be organized this way, with structured and unstructured regions that work together.


'"/>

Source:Huntsman Cancer Institute/University of Utah Health Sciences Center


Related biology news :

1. Scientists ID molecular switch in liver that triggers harmful effects of saturated and trans fats
2. Molecular on/off switch controls immune defenses against viruses
3. Scientists find potential off-switch for HIV virus
4. Discovery of master switch for the communication process between chloroplast and nuclei of plants
5. Scientists document complex genomic events leading to the birth of new genes
6. Advances in the characterisation of the oyster mushroom genes
7. Compounds in plastic packaging act as environmental estrogens altering breast genes
8. Where bacteria get their genes
9. NYU, Rockefeller researchers find complexity of regulation by microRNA genes
10. Exercise training in ordinary people affects the activity of 500 genes
11. Carnegie Mellon University research reveals how cells process large genes
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:3/28/2017)... , March 28, 2017 The ... Hardware (Camera, Monitors, Servers, Storage Devices), Software (Video Analytics, ... Region - Global Forecast to 2022", published by MarketsandMarkets, ... 2016 and is projected to reach USD 75.64 Billion ... and 2022. The base year considered for the study ...
(Date:3/24/2017)... March 24, 2017 The Controller General of Immigration ... Abdulla Algeen have received the prestigious international IAIR Award for ... Continue Reading ... ... Deputy Controller Abdulla Algeen (small picture on the right) have received the ...
(Date:3/23/2017)... PUNE, India , March 23, 2017 The report ... Equipment, Touchless Biometric), Industry, and Geography - Global Forecast to 2022", published by ... growing at a CAGR of 29.63% between 2017 and 2022. ... ... Logo ...
Breaking Biology News(10 mins):
(Date:6/16/2017)... ... 16, 2017 , ... CTNext , Connecticut’s go-to resource for entrepreneurial support, ... LOFT at Chelsea Piers in Stamford. , Nine finalists, all of whom are Connecticut-based ... an opportunity to secure $10,000 awards to help support business growth. The winners included:, ...
(Date:6/15/2017)... ... June 15, 2017 , ... ... promising new medical device startup. Dan Parsley, angelMD’s SVP of Corporate Development, served ... and this angelMD syndicate is part of Saranas’ recently announced $4 million Series ...
(Date:6/14/2017)... ... 14, 2017 , ... The Thailand Board of Investment (BOI) ... co-hosting a delegation from Thailand at BIO 2017 in San Diego, CA taking ... the world, regroups more than 1,100 biotech companies, academic institutions, state biotechnology centers ...
(Date:6/14/2017)... ... 2017 , ... The newest company to join the Science Center’s Port business ... human genes. ATGC, a spin out of the University of Michigan, will occupy lab ... genomics company. Its founders are among the first wave of researchers adopting into ...
Breaking Biology Technology: