Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Dynamics of crucial protein 'switch' revealed

18.05.2011
Cell signaling networks tied to diabetes and cancer

Researchers at the University of Texas Medical Branch at Galveston and the University of California-San Diego School of Medicine have published a study that offers a new understanding of a protein critical to physiological processes involved in major diseases such as diabetes and cancer. This work could help scientists design drugs to battle these disorders.

The article was deemed a "Paper of the Week" by and will be on the cover of the Journal of Biological Chemistry. It is scheduled for publication May 20 and now available online.

"This study applied a powerful protein structural analysis approach to investigate how a chemical signal called cAMP turns on one of its protein switches, Epac2," said principal investigator Xiaodong Cheng, professor in the Department of Pharmacology and Toxicology and member of the Sealy Center for Structural Biology and Molecular Biophysics at UTMB.

The cAMP molecule controls many physiological processes, ranging from learning and memory in the brain and contractility and relaxation in the heart to insulin secretion in the pancreas. cAMP exerts its action in cells by binding to and switching on specific receptor proteins, which, when activated by cAMP, turn on additional signaling pathways.

Errors in cell signaling are responsible for diseases such as diabetes, cancer and heart failure. Understanding cAMP-mediated cell signaling, in which Epac2 is a major player, likely will facilitate the development of new therapeutic strategies specifically targeting the cAMP-Epac2 signaling components, according to the researchers.

The project involved an ongoing collaboration between Cheng's research group at UTMB, experts in the study of cAMP signaling, and UCSD professor of medicine Virgil Woods Jr. and colleagues at UCSD, pioneers in the development and application of hydrogen/deuterium exchange mass spectrometry (DXMS) technology. Compared with other protein-analysis techniques, DXMS is especially good at studying the structural motion of proteins.

Using this novel approach, the investigators were able to reveal, in fine detail, that cAMP interacts with its two known binding sites on Epac2 in a sequential fashion and that binding of cAMP changes the shape of the protein in a very specific way – switching on its activity by exposing further signaling interaction sites on Epac2.

"DXMS analysis has proved to be an amazingly powerful approach, alone or in combination with other techniques, in figuring out how proteins work as molecular machines, changing their shapes – or morphing – in the normal course of their function," said Woods. "This will be of great use in the identification and development of therapeutic drugs that target these protein motions."

Collaborators include Tamara Tsalkova and Fang Mei of the UTMB Department of Pharmacology and Toxicology; Mark A. White, associate professor in the UTMB Department of Biochemistry and Molecular Biology; and Dr. Sheng Li, Dr. Tong Liu and Daphne Wang of the UCSD Department of Medicine and Biomedical Sciences Graduate Program.

The study was funded by the National Institutes of Health and the John Sealy Memorial Endowment Fund for Biomedical Research. Based on its success at applying DXMS to the analysis of a number of important proteins, exemplified by this study with UTMB researchers, UCSD recently was awarded a generous NIH grant to implement "next-generation" advanced DXMS analysis for the benefit of scientists throughout the United States.

Photographs: http://bit.ly/kxhNeJ, http://bit.ly/jCzZSr, http://bit.ly/lEEU5d

Molly Dannenmaier | EurekAlert!
Further information:
http://www.utmb.edu

More articles from Life Sciences:

nachricht Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory

nachricht Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

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...

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

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>