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 Rutgers scientists discover 'Legos of life'
23.01.2018 | Rutgers University

nachricht Researchers identify a protein that keeps metastatic breast cancer cells dormant
23.01.2018 | Institute for Research in Biomedicine (IRB Barcelona)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Optical Nanoscope Allows Imaging of Quantum Dots

Physicists have developed a technique based on optical microscopy that can be used to create images of atoms on the nanoscale. In particular, the new method allows the imaging of quantum dots in a semiconductor chip. Together with colleagues from the University of Bochum, scientists from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute reported the findings in the journal Nature Photonics.

Microscopes allow us to see structures that are otherwise invisible to the human eye. However, conventional optical microscopes cannot be used to image...

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Rutgers scientists discover 'Legos of life'

23.01.2018 | Life Sciences

Seabed mining could destroy ecosystems

23.01.2018 | Earth Sciences

Transportable laser

23.01.2018 | Physics and Astronomy

VideoLinks Science & Research
Overview of more VideoLinks >>>