Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein Shake-Up

27.03.2015

Researchers use neutron scattering and supercomputing to study shape of a protein involved in cancer

For living organisms proteins are an essential part of their body system and are needed to thrive. In recent years, a certain class of proteins has challenged researchers’ conventional notion that proteins have a static and well-defined structure.


ORNL

ORNL researchers are using neutrons and modeling to better understand the beta-catenin protein (pictured is the structure of the protein's armadillo repeat region). Disordered regions known as the N-terminal and C-terminal tails (not shown) are thought to interact dynamically with the armadillo repeat region. Characterizing the structural ensemble of the disordered regions is necessary toward understanding their interactions and hence, their function.

It’s thought that mutations in these proteins, known as intrinsically disordered proteins, are associated with neurodegenerative changes, cardiovascular disorders and diseases such as diabetes and cancer. A better understanding of these proteins could have major implications in the energy, environmental and health biosciences.

One intrinsically disordered protein, beta-catenin, is of particular interest to researchers at the Department of Energy’s Oak Ridge National Laboratory, where they will be conducting neutron scattering and supercomputing studies to further uncover its role in cancer.

“This protein violates everything we know about proteins,” says Arvind Ramanathan of ORNL’s Computational Data Analytics Group. “It doesn’t have a very stable secondary structure except for a small region which forms a kidney bean shape.”

“What we proposed to do is to take a look at the protein using neutron scattering and combine the data with large scale simulation of this molecule utilizing supercomputing capabilities at ORNL,” he says.

The joint research project started after ORNL, Georgetown and Howard Universities, Washington Veteran’s Affairs Medical Center and MedStar Research Institute won a Clinical Translation Science Award. The award is funded by the National Center for Advancing Translation Science, one of the institutes at the National Institutes of Health.

The beta-catenin protein occurs naturally in the body and is active in a pathway that sends signals from outside a cell to the inside of a cell. One of its terminal ends responds to cancer, and researchers have observed negative effects during cancer if changes occur to this side.

“Mutations in this protein usually impact drug resistance, relapse of cancers and many other important functional cellular roles during cancer,” Ramanathan says.

To gain insight and a better idea of what beta-catenin’s shape is and how the shape changes under various circumstances, the researchers plan to use neutron scattering techniques on ORNL’s Spallation Neutron Source’s EQ-SANS instrument.

“On the neutron side, we are doing experiments that will allow us to characterize in very great detail how the protein changes its shape,” Ramanathan says.

The data from the neutron experiments will then be analyzed using the supercomputing capabilities at DOE's Oak Ridge Leadership Computing Facility at ORNL. Additionally, the researchers will run simulations and model the protein while looking at other proteins to detect and characterize the protein’s cancer responding terminal.

What they learn from the study will help them understand how the B-catenin protein binds to its partner cells and how the process changes after a mutation has occurred, which is often associated with cancer.

“If we don’t understand how the protein binds specifically to certain signaling partners, we wouldn’t know how to distinguish what its function is in a cancer related pathway versus a functional pathway,” Ramanathan says.

The National Institutes of Health and National Center for Advancing Translation Science is providing funding for the study. The research involves the Spallation Neutron Source and the Oak Ridge Leadership Computing Facility, which are DOE Office of Science User Facilities.

UT-Battelle manages ORNL for the Department of Energy's Office of Science. The Office of Science is the single largest supporter of basic research in the physical sciences in the United States, and is working to address some of the most pressing challenges of our time. For more information, please visit http://science.energy.gov/ .- By Chris Samoray

Image: ORNL researchers are using neutrons and modeling to better understand the beta-catenin protein (pictured is the structure of the protein's armadillo repeat region). Disordered regions known as the N-terminal and C-terminal tails (not shown) are thought to interact dynamically with the armadillo repeat region. Characterizing the structural ensemble of the disordered regions is necessary toward understanding their interactions and hence, their function.

Contact Information
Chris Samoray
samoraycr@ornl.gov
865-241-0709

Chris Samoray | newswise
Further information:
http://www.ornl.gov/news

Further reports about: Computing Facility ORNL Protein Spallation beta-catenin neutron scattering pathway structure

More articles from Life Sciences:

nachricht Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY

nachricht NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

Global study of world's beaches shows threat to protected areas

19.07.2018 | Earth Sciences

New creepy, crawly search and rescue robot developed at Ben-Gurion U

19.07.2018 | Power and Electrical Engineering

Metal too 'gummy' to cut? Draw on it with a Sharpie or glue stick, science says

19.07.2018 | Materials Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>