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 Fingerprint' technique spots frog populations at risk from pollution
27.03.2017 | Lancaster University

nachricht Parallel computation provides deeper insight into brain function
27.03.2017 | Okinawa Institute of Science and Technology (OIST) Graduate University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Northern oceans pumped CO2 into the atmosphere

27.03.2017 | Earth Sciences

Fingerprint' technique spots frog populations at risk from pollution

27.03.2017 | Life Sciences

Big data approach to predict protein structure

27.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>