Using X-rays and neutron beams, a team of researchers from the University of California, San Diego School of Medicine, University of Utah and Oak Ridge National Laboratory have teased out new information about Protein Kinase A (PKA), a ubiquitous master switch that helps regulate fundamental cellular functions like energy consumption and interactions with hormones, neurotransmitters and drugs.
"Mutations in PKA can lead to a variety of different human diseases, including cancers, metabolic and cardiovascular diseases and diseases involving the brain and nervous system," said senior author Susan Taylor, PhD, professor of chemistry, biochemistry and pharmacology at UC San Diego and international authority on PKA. "Developing treatments and cures for these diseases depends upon knowing how the switch works."
Writing in the October 10 issue of the Journal of Biological Chemistry, Taylor and colleagues focused on one of four forms of PKA called "II-beta," which is found mostly in the brain and in fat, where it may play an important role in obesity and diet-induced insulin-resistance associated with type 2 diabetes.
All forms of PKA are controlled by a signaling molecule called cyclic AMP or cAMP. Many cellular functions are based upon changing amounts of cAMP within cells. PKA is the molecular sensor for cAMP, modulating cell activity according to cAMP levels.
The scientists investigated which parts of the II-beta protein were needed to determine its overall shape, internal architecture and ability to change shape – factors that dictate function. II-beta is very compact when inactive but extends and separates into subunits when it senses cAMP.
"A key question regarding the architecture of the II-beta was whether both of its cAMP-sensing mechanisms were needed for the unique changes in shape that it undergoes with cAMP," said first author Donald K. Blumenthal, PhD, associate professor of pharmacology and toxicology at the University of Utah College of Pharmacy.
Researchers removed one of II-beta's cAMP sensors and then documented its ability to change shape in response to cAMP, using small-angle X-ray and advanced neutron scattering imaging technologies at Oak Ridge's High Flux Isotope Reactor in Tennessee. They found the protein could still change shape with just one sensor and that its internal architecture remained similar to II-beta protein with both its cAMP sensors.
The findings further narrow and define the key components of II-beta and identify new regions for further investigation. Taylor said the collaborative, multi-team effort also demonstrated the importance of using different techniques in an iterative way to unravel the dynamic properties of complex systems.
Co-authors include Jeffrey Copps, Eric V. Smith-Nguyen and Ping Zhang, UCSD Department of Chemistry and Biochemistry and Howard Hughes Medical Institute; and William T. Heller, Oak Ridge National Laboratory.
Funding support for this research came, in part, from the U.S. Department of Energy and the National Institutes of Health (grant GM34921).
Scott LaFee | Eurek Alert!
Decoding the genome's cryptic language
27.02.2017 | University of California - San Diego
New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg
On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.
On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
27.02.2017 | Materials Sciences
27.02.2017 | Interdisciplinary Research
27.02.2017 | Life Sciences