The conventional wisdom was that the job of turning proteins on and off -- and thus determining their actions -- fell to phosphates, in a common and easy-to-detect chemical step in which phosphates fasten to and unfasten from proteins; a process called phosphorylation.
Now, after decades of investigating the "new" sugar-based protein modification they discovered, the Johns Hopkins team admits that they themselves were surprised by their latest results. Published recently in the Proceedings of the National Academy of Sciences, their findings show that the surreptitious sugar switch is likely as influential and ubiquitous as its phosphate counterpart and, indeed, even plays a role in regulating phosphorylation itself.
More to the point, the work has implications for finding new treatments for a number of diseases such as diabetes, neurodegeneration and cancer, because the new switches form yet another potential target for manipulation by drugs.
"Like dark matter in the cosmos, it's hard to find even though it's very abundant," says Gerald Hart, Ph.D., the DeLamar Professor and director of biological chemistry at the Johns Hopkins School of Medicine, referring to the sugar (O-GlcNAc, pronounced oh-GLICK-nac) that carries out GlcNAcylation.
For years, Hart's team thought of GlcNAcylation as phosphorylation's foil; a simple, classic case of either-or. New technologies involving molecular sleuthing with a mass spectrometer allowed them to measure the extent to which the addition of sugar to proteins affects phosphorylation.
Of 428 sites on which phosphate was being added to and taken off of proteins, all responded in some way to increased O-GlcNAc: 280 decreased phosphorylation and 148 increased phosphorylation.
"The influence of sugar is striking," Hart says. "The presence of O-GlcNAc causes the enzymes that add the phosphate to do something different, and this cross-talk itself can modify proteins."
Because both sugar and phosphate modifications are linked to how cells work, they are fundamental to understanding and eventual control of the molecular processes that underlie many diseases.
"With regard to cancer, diabetes and Alzheimer's," says Hart, "most people in the world today have been studying the yang (phosphorylation) but not the yin (GlcNAcylation). There's another whole side that people were unaware of where diabetes diagnostics and cancer therapies could be targeted."
The research was funded by the National Institutes of Health.
Authors on the paper are Zihao Wang, Marjan Gucek and Gerald W. Hart, all of Johns Hopkins.
Maryalice Yakutchik | EurekAlert!
Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo
Research reveals how order first appears in liquid crystals
23.05.2018 | Brown University
At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.
At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...
There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?
At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...
So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics
Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...
The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...
A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.
The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...
02.05.2018 | Event News
13.04.2018 | Event News
12.04.2018 | Event News
23.05.2018 | Life Sciences
23.05.2018 | Life Sciences
23.05.2018 | Physics and Astronomy