Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Just a Little Squeeze Lets Proteins Assess DNA

18.12.2008
To find its target, all a protein needs to do is give quick squeezes as it moves along the DNA strand, suggests new research from The University of Arizona in Tucson.

Scientists had thought DNA-binding proteins primarily used full-body hugs for accurate readings of the information coded in the DNA's sequence.

Even a protein known to use the hug method, called direct readout, can effectively pinpoint sites on DNA using indirect readout, found researcher Nancy C. Horton and her colleagues.

"It was a total surprise," said Horton, a UA associate professor of biochemistry and molecular biophysics. "No one had ever seen it before."

Doing the quick squeezes that scientists call indirect readout probably works faster than requiring full-body contact with all the DNA, the researchers suggest. Quick and accurate identification of key sites on DNA is important for the health of all kinds of cells, from bacteria to humans.

To detect the protein-DNA connection in such detail, Horton and her co-authors Elizabeth J. Little and Andrea C. Babic studied a DNA-binding protein that bacteria use to protect themselves from viral infections.

The finding has implications for the development of designer drugs.

"People have and are developing DNA-binding proteins to turn genes on and off," Horton said. Such designer proteins can be used to cut out the bad copy of a gene and help replace it with good copy.

"We found that indirect readout is important for finding the right sequence, and we now think indirect readout is also important for finding it quickly,"

she said.

The team published their paper, "Early Interrogation and Recognition of DNA Sequence by Indirect Readout," in the December issue of the journal Structure. First author Little and co-author Babic were postdoctoral research associates in Horton's laboratory when they did the research. The two are now senior scientists at Ventana Medical Systems, Inc. in Tucson, Ariz.

The National Institutes of Health funded the research.

Horton studies proteins that bind to DNA.

Seven years ago, she figured out the structure of a protein called HincII that snips up DNA. The protein is a type of enzyme called a restriction endonuclease and comes from Haemophilus influenzae bacteria.

Since that time, Horton has been trying to learn how HincII interrogates the DNA to find the right place to cut.

The protein protects bacteria by cutting up DNA from invading viruses.
Without the protective protein, viral DNA would commandeer the bacterium's cellular machinery to produce viruses and ultimately kill the bacterial cell.

The HincII protein distinguishes between bacterial DNA and viral DNA by recognizing certain sequences on DNA. Such a defense requires speed to prevent the marauding virus from killing the cell and also accuracy so the protein doesn't accidentally hack up the bacterium's own DNA.

Horton knew from her previous work that the HincII protein used the direct readout method to find the particular sequence of DNA that corresponded to enemy DNA. The protein seemed to distort the DNA to read it.

Removing the direct readout contact between the protein and the DNA might show whether the DNA distortion or the contact itself was important, Horton said.

Therefore Little and Babic created a mutant protein that couldn't hug DNA closely and therefore couldn't use the direct readout method. Little described the mutant protein as missing the fingers the normal protein used to probe the DNA.

"If the finger was doing all the recognition, then the mutant should cut any DNA sequence," Horton said.

To see how the mutant interacted with DNA, the researchers crystallized the mutant protein-DNA complex in action.

Initially, Horton thought the assay had gone wrong and almost threw the results in the trash, she wrote in an e-mail.

The mutant protein had chosen the proper site on the DNA with 100 percent specificity, which was opposite from what she expected. In addition, the DNA was distorted, even though the mutant couldn't make the strong contact a normal protein would.

"I did a double-take. I was just taking a picture to have a record that it was non-specific," she said.

Understanding how endonucleases and other DNA binding-proteins recognize a particular DNA sequence provides insight into key cellular processes including the replication, transcription and repair of DNA.

Little said, "In every single one of your cells are proteins looking for the proper sequences in DNA in order to make the proteins you need to stay alive."

Horton added, "Understanding how these processes work helps in the understanding of diseases so that we could potentially cure the disease."

Researcher contact information:
Nancy C. Horton
Associate Professor of Biochemistry and Molecular Biophysics nhorton@u.arizona.edu
520-626-3828 (office)
520-626-0246 (lab)

Mari N. Jensen | The University of Arizona
Further information:
http://www.arizona.edu

More articles from Life Sciences:

nachricht Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>