Featured Research

from universities, journals, and other organizations

'Jekyll and Hyde' protein linked to type 1 diabetes

Date:
June 9, 2014
Source:
Monash University
Summary:
Researchers are a step closer to establishing the link between a protein with a split personality and type 1 diabetes. New research shows how a protein, called GAD65, changes its shape when it turns itself on and off. Curiously, this characteristic may also link it to type 1 diabetes. In the human brain, GAD65 performs an essential role, making 'neurotransmitters,' chemicals that pass messages between brain cells.

Researchers are a step closer to establishing the link between a protein with a split personality and type 1 diabetes.

New research, published in the journal PNAS, shows how a protein, called GAD65, changes its shape when it turns itself on and off. Curiously, this characteristic may also link it to type 1 diabetes.

In the human brain, GAD65 performs an essential role: it makes 'neurotransmitters' -- chemicals that pass messages between brain cells.

GAD65 is also found in the pancreas. Previous studies linked it to type 1 diabetes because the body makes antibodies against the protein. However the molecular details of what makes GAD65 'sticky' to antibodies has remained a mystery until now.

The new research, led by Monash University, investigated how GAD65 regulates the production of neurotransmitters by changing its shape.

Principal Investigator Associate Professor Ashley Buckle said the findings showed that the normal function of the protein may come at a price.

"GAD65 has an unpredictable, almost Jekyll and Hyde personality when it is turned on and off. When active and making neurotransmitters, it is rigid and rather motionless. Ironically, when switched off, rather than resting as you might expect, it becomes mobile, dancing and jiggling around.

"We suspected that this dual personality might affect how antibodies 'see' it. This turns out to be true -- antibodies interact with it very differently depending on whether it's on or off," Associate Professor Buckle said.

GAD65 has previously been used in clinical trials as a vaccine for type 1 diabetes, with limited success. Associate Professor Buckle said the discovery may ultimately lead to the development of better vaccines to potentially treat and prevent type 1 diabetes.

"The idea to immunize an individual with GAD65 to help the immune system develop a tolerance against it, to stop or at least dampen the immune reaction is a good one. But so far these attempts have not been very successful. This research could change that," Associate Professor Buckle said.

The seven-year study used a combination of experimental and computational methods to understand what GAD65 looks like in its 'off' state and how human antibodies interact with both forms.

Powerful beam lines at the Australian Synchrotron, as well as massive super computers at the Victorian Life Sciences Computation Initiative (VLSCI) and Monash, were used to accelerate the research.

Associate Professor Buckle said access to world-class facilities was critical to the research.

"Techniques like X-ray crystallography produce amazing, detailed pictures of large molecules, but these are often snapshots frozen in time. In order to 'see' the molecules in action we needed to combine other techniques, such as molecular simulation, to produce a movie. The Australian Synchrotron and the VLSCI played a major part in this work," Associate Professor Buckle said.

In the next phase, the research team will visualize GAD65 as it interacts with a human antibody. Understanding why GAD65 is recognised and targeted by antibodies is the next step. In addition to specific insights, it's hoped this work will provide important basic knowledge that could be applied to broader aspects of health and medicine.


Story Source:

The above story is based on materials provided by Monash University. Note: Materials may be edited for content and length.


Journal Reference:

  1. I. Kass, D. E. Hoke, M. G. S. Costa, C. F. Reboul, B. T. Porebski, N. P. Cowieson, H. Leh, E. Pennacchietti, J. McCoey, O. Kleifeld, C. Borri Voltattorni, D. Langley, B. Roome, I. R. Mackay, D. Christ, D. Perahia, M. Buckle, A. Paiardini, D. De Biase, A. M. Buckle. Cofactor-dependent conformational heterogeneity of GAD65 and its role in autoimmunity and neurotransmitter homeostasis. Proceedings of the National Academy of Sciences, 2014; DOI: 10.1073/pnas.1403182111

Cite This Page:

Monash University. "'Jekyll and Hyde' protein linked to type 1 diabetes." ScienceDaily. ScienceDaily, 9 June 2014. <www.sciencedaily.com/releases/2014/06/140609161735.htm>.
Monash University. (2014, June 9). 'Jekyll and Hyde' protein linked to type 1 diabetes. ScienceDaily. Retrieved August 21, 2014 from www.sciencedaily.com/releases/2014/06/140609161735.htm
Monash University. "'Jekyll and Hyde' protein linked to type 1 diabetes." ScienceDaily. www.sciencedaily.com/releases/2014/06/140609161735.htm (accessed August 21, 2014).

Share This




More Health & Medicine News

Thursday, August 21, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Drug Used To Treat 'Ebola's Cousin' Shows Promise

Newsy (Aug. 21, 2014) An experimental drug used to treat Marburg virus in rhesus monkeys could give new insight into a similar treatment for Ebola. Video provided by Newsy
Powered by NewsLook.com
Cadavers, a Teen, and a Medical School Dream

Cadavers, a Teen, and a Medical School Dream

AP (Aug. 21, 2014) Contains graphic content. He's only 17. But Johntrell Bowles has wanted to be a doctor from a young age, despite the odds against him. He was recently the youngest participant in a cadaver program at the Indiana University NW medical school. (Aug. 21) Video provided by AP
Powered by NewsLook.com
American Ebola Patients Released: What Cured Them?

American Ebola Patients Released: What Cured Them?

Newsy (Aug. 21, 2014) It's unclear whether the American Ebola patients' recoveries can be attributed to an experimental drug or early detection and good medical care. Video provided by Newsy
Powered by NewsLook.com
Lost Brain Cells To Blame For Sleep Problems Among Seniors

Lost Brain Cells To Blame For Sleep Problems Among Seniors

Newsy (Aug. 21, 2014) According to a new study, elderly people might have trouble sleeping because of the loss of a certain group of neurons in the brain. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins