Corporate Banner
Satellite Banner
Proteomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Team Reveals Key Protein Interactions Involved in Neurodegenerative Disease

Published: Thursday, November 15, 2012
Last Updated: Thursday, November 15, 2012
Bookmark and Share
New study reveals the structure of c-jun-N-terminal kinases (JNK) enzymes.

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have defined the molecular structure of an enzyme as it interacts with several proteins involved in outcomes that can influence neurodegenerative disease and insulin resistance.

The enzymes in question, which play a critical role in nerve cell (neuron) survival, are among the most prized targets for drugs to treat brain disorders such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis (ALS).

The study was published online ahead of print on November 8, 2012, by the journal Structure.

The new study reveals the structure of a class of enzymes called c-jun-N-terminal kinases (JNK) when bound to three peptides from different protein families; JNK is an important contributor to stress-induced apoptosis (cell death), and several studies in animal models have shown that JNK inhibition protects against neurodegeneration.

“Our findings have long-range implications for drug discovery,” said TSRI Professor Philip LoGrasso, who, along with TSRI Associate Professor Kendall Nettles, led the study.

Professor Nettles continued, “Knowing the structure of JNK bound to these proteins will allow us to make novel substrate competitive inhibitors for this enzyme with even greater specificity and hopefully less toxicity.”

The scientists used what they called structure class analysis, looking at groups of structures, which revealed subtle differences not apparent looking at them individually.

“From a structural point of view, these different proteins appear to be very similar, but the biochemistry shows that the results of their binding to JNK were very different,” he said.

LoGrasso and his colleagues were responsible for creating and solving the crystal structures of the three peptides (JIP1, SAB, and ATF-2) with JNK3 using a technique called x-ray crystallography, while Nettles handled much of the data analysis.

All three peptides have important effects, LoGrasso said, inducing two distinct inhibitory mechanisms-one where the peptide caused the activation loop to bind directly in the ATP pocket, and another with allosteric control (that is, using a location on the protein other than the active site). Because JNK signaling needs to be tightly controlled, even small changes in it can alter a cell’s fate.

“Solving the crystal structures of these three bound peptides gives us a clearer idea of how we can block each of these mechanisms related to cell death and survival,” LoGrasso said. “You have to know their structure to know how to deal with them.”


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Scripps Scientists Awarded NIH Grant for Biomarker Studies
$2.3 million grant awarded to develop new diagnostics for cancer, rheumatoid arthritis, colitis.
Tuesday, May 06, 2014
Scientists Solve 40-year Mystery of How Sodium Controls Opioid Brain Signaling
The findings pave way for new therapies for treating pain and mood disorders.
Thursday, January 16, 2014
Scientists Discover a New Type of Protein Modification that May Play a Role in Cancer and Diabetes
Scientists at The Scripps Research Institute (TSRI) have discovered a new type of chemical modification that affects numerous proteins within mammalian cells.
Tuesday, August 06, 2013
Chemists Devise Inexpensive, Benchtop Method for Marking and Selecting Cells
Chemists at The Scripps Research Institute have found an easier way to perform one of the most fundamental tasks in molecular biology.
Wednesday, January 16, 2013
Scientists Discover How Two Proteins Help Keep Cells Healthy
The work has implications for cancer drug development.
Thursday, December 06, 2012
Scientists Find Structure of a Protein that Makes Cancer Cells Resistant to Chemotherapy
A research team at the Scripps Research Institute has obtained the first glimpse of a protein that keeps certain substances, including many drugs, out of cells.
Monday, March 30, 2009
Scientific News
TOPLESS Plants Provide Clues to Human Molecular Interactions
Scientists at Van Andel Research Institute have revealed an important molecular mechanism in plants that has significant similarities to certain signaling mechanisms in humans, which are closely linked to early embryonic development and to diseases such as cancer.
Toxin from Salmonid Fish has Potential to Treat Cancer
Researchers from the University of Freiburg decode molecular mechanism of fish pathogen.
Study Finds Non-Genetic Cancer Mechanism
Cancer can be caused solely by protein imbalances within cells, a study of ovarian cancer has found.
Long-sought Discovery Fills in Missing Details of Cell 'Switchboard'
A biomedical breakthrough reveals never-before-seen details of the human body’s cellular switchboard that regulates sensory and hormonal responses.
Rice Disease-Resistance Discovery Closes the Loop for Scientific Integrity
Researchers reveal how disease resistant rice detects and responds to bacterial infections.
The Mystery of the Instant Noodle Chromosomes
Researchers from the Lomonosov Moscow State University evaluated the benefits of placing the DNA on the principle of spaghetti.
New Mussel-Inspired Surgical Protein Glue
Korean scientists have developed a light-activated, mussel protein-based bioadhesive that works on the same principles as mussels attaching to underwater surfaces and insects maintaining structural balance and flexibility.
Vital Protein in Healthy Fertilization Process Identified
Researchers at the National Institutes of Health have discovered a protein that plays a vital role in healthy egg-sperm union in mice.
Teeth Reveal Lifetime Exposures to Metals, Toxins
Researchers have identified dental biomarkers to reveal links between early iron exposure and late life brain diseases.
View of Bacterial Pump at the Atomic Level
Researchers have determined the structure of a simple but previously unexamined pump that controls the passage of proteins through a bacterial cell membrane, an achievement that offers new insight into the mechanics that allow bacteria to manipulate their environments.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!