Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Sorting out the Structure of a Parkinson’s Protein

Published: Tuesday, April 02, 2013
Last Updated: Tuesday, April 02, 2013
Bookmark and Share
Computer modeling may resolve conflicting results and offer hints for new drug-design strategies.

Clumps of proteins that accumulate in brain cells are a hallmark of neurological diseases such as dementia, Parkinson’s disease and Alzheimer’s disease. Over the past several years, there has been much controversy over the structure of one of those proteins, known as alpha synuclein.

MIT computational scientists have now modeled the structure of that protein, most commonly associated with Parkinson’s, and found that it can take on either of two proposed states — floppy or rigid. The findings suggest that forcing the protein to switch to the rigid structure, which does not aggregate, could offer a new way to treat Parkinson’s, says Collin Stultz, an associate professor of electrical engineering and computer science at MIT.

“If alpha synuclein can really adopt this ordered structure that does not aggregate, you could imagine a drug-design strategy that stabilizes these ordered structures to prevent them from aggregating,” says Stultz, who is the senior author of a paper describing the findings in a recent issue of the Journal of the American Chemical Society.

For decades, scientists have believed that alpha synuclein, which forms clumps known as Lewy bodies in brain cells and other neurons, is inherently disordered and floppy. However, in 2011 Harvard University neurologist Dennis Selkoe and colleagues reported that after carefully extracting alpha synuclein from cells, they found it to have a very well-defined, folded structure.

That surprising finding set off a scientific controversy. Some tried and failed to replicate the finding, but scientists at Brandeis University, led by Thomas Pochapsky and Gregory Petsko, also found folded (or ordered) structures in the alpha synuclein protein.

Stultz and his group decided to jump into the fray, working with Pochapsky’s lab, and developed a computer-modeling approach to predict what kind of structures the protein might take. Working with the structural data obtained by the Brandeis researchers, Stultz created a model that calculates the probabilities of many different possible structures, to determine what set of structures would best explain the experimental data.

The calculations suggest that the protein can rapidly switch among many different conformations. At any given time, about 70 percent of individual proteins will be in one of the many possible disordered states, which exist as single molecules of the alpha synuclein protein. When three or four of the proteins join together, they can assume a mix of possible rigid structures, including helices and beta strands (protein chains that can link together to form sheets).

“On the one hand, the people who say it’s disordered are right, because a majority of the protein is disordered,” Stultz says. “And the people who would say that it’s ordered are not wrong; it’s just a very small fraction of the protein that is ordered.”

The MIT researchers also found that when alpha synuclein adopts an ordered structure, similar to that described by Selkoe and co-workers, the portions of the protein that tend to aggregate with other molecules are buried deep within the structure, explaining why those ordered forms do not clump together.

Stultz is now working to figure out what controls the protein’s configuration. There is some evidence that other molecules in the cell can modify alpha synuclein, forcing it to assume one conformation or another.

“If this structure really does exist, we have a new way now of potentially designing drugs that will prevent aggregation of alpha synuclein,” he says.

Lead author of the paper is Thomas Gurry, an MIT graduate student in computational and systems biology. Other authors are Orly Ullman, an MIT graduate student in chemistry; Pochapsky, a professor of chemistry and biochemistry at Brandeis; Iva Perovic, a graduate student in Pochapsky’s lab; and Charles Fisher, a Harvard graduate student in biophysics.

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 2,600+ scientific posters on ePosters
  • More Than 3,800+ 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 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

Messing With The Monsoon
Manmade aerosols can alter rainfall in the world’s most populous region.
Friday, October 02, 2015
A Natural Light Switch
MIT scientists identify and map the protein behind a light-sensing mechanism.
Tuesday, September 29, 2015
Biologists Find Unexpected Role for Amyloid-Forming Protein
Yeast protein could offer clues to how Alzheimer’s plaques form in the brain.
Monday, September 28, 2015
How Flu Viruses Gain The Ability To Spread
New study reveals the soft palate is a key site for evolution of airborne transmissibility.
Friday, September 25, 2015
Viruses Join Fight Against Harmful Bacteria
Engineered viruses could combat human disease and improve food safety.
Friday, September 25, 2015
Targeting DNA
Protein-based sensor could detect viral infection or kill cancer cells.
Tuesday, September 22, 2015
Targeting DNA
Protein-based sensor could detect viral infection or kill cancer cells.
Tuesday, September 22, 2015
Personalized Heart Models For Surgical Planning
System can convert MRI scans into 3D-printed, physical models in a few hours.
Friday, September 18, 2015
Learning About Human Health Using Sewage
PhD student Mariana Matus studies human waste to understand individual and community health.
Thursday, September 17, 2015
Intensity of Desert Storms May Affect Ocean Phytoplankton
MIT study finds phytoplankton are extremely sensitive to changing levels of desert dust.
Tuesday, September 01, 2015
Searching Big Data Faster
Theoretical analysis could expand applications of accelerated searching in biology, other fields.
Thursday, August 27, 2015
Protein Found to Play a Key Role in Blocking Pathogen Survival
Calprotectin fends off microbial invaders by limiting access to iron, an important nutrient.
Wednesday, August 26, 2015
A Metabolic Master Switch Underlying Human Obesity
Researchers find pathway that controls metabolism by prompting fat cells to store or burn fat.
Friday, August 21, 2015
Capturing Cell Growth in 3-D
Spinout’s microfluidics device better models how cancer and other cells interact in the body.
Monday, August 17, 2015
Better Estimates of Worldwide Mercury Pollution
New findings show Asia produces twice as much mercury emissions as previously thought.
Thursday, August 13, 2015
Scientific News
Michigan Researchers Use Raman Spectroscopy
inVia confocal Raman microscope used in the study of various childhood diseases.
Genetic Defences of Bacteria Don’t Aid Antibiotic Resistance
Genetic responses to the stresses caused by antibiotics don’t help bacteria to evolve a resistance to the medications, according to a new study by Oxford University researchers.
Detecting HIV Diagnostic Antibodies with DNA Nanomachines
New research may revolutionize the slow, cumbersome and expensive process of detecting the antibodies that can help with the diagnosis of infectious and auto-immune diseases such as rheumatoid arthritis and HIV.
Snapshot Turns T Cell Immunology on its Head
New research may have implications for 1 diabetes sufferers.
Tolerant Immune System Increases Cancer Risk
Researchers have found that individuals with high immunoCRIT ratios may have an increased risk of developing certain cancers.
Developing a Gel that Mimics Human Breast for Cancer Research
Scientists at the Universities of Manchester and Nottingham have been funded to develop a gel that will match many of the biological structures of human breast tissue, to advance cancer research and reduce animal testing.
Cell's Waste Disposal System Regulates Body Clock Proteins
New way to identify interacting proteins could identify potential drug targets.
New Approach to Treating Heparin-induced Blood Disorder
A potential treatment for a serious clotting condition that can strike patients who receive heparin to treat or prevent blood clots may lie within reach by elucidating the structure of the protein complex at its root.
Horse Illness Shares Signs of Human Disease
Horses with a rare nerve condition have similar signs of disease as people with conditions such as Alzheimer’s, a study has found.
How a Molecular Motor Untangles Protein
Diseases such as Alzheimer’s, Parkinson’s and prion diseases, all involve “tangled” proteins.
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
2,600+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,800+ scientific videos