Shining light on amyloid protein nanostructures

August 14, 2012
UT Research on cover of Angewandte Chemie
The research team recently published their results in the leading scientific journal Angewandte Chemie, which highlighted this work on the cover of the journal.

Scientists from the MESA+ and MIRA research institutes at the University of Twente have developed a new method to gain insight into the composition of large macromolecular protein assemblies. Their method allows the determination of the composition of potentially toxic amyloid protein assemblies involved in many human neurodegenerative diseases. The research team recently published their results in the leading scientific journal Angewandte Chemie, which highlighted this work on the cover of the journal.

Many human , such as Parkinson’s disease, Alzheimer’s disease, or Huntington’s disease, are the result of protein misfolding. As a result of this misfolding, the monomeric proteins can aggregate and form small protein clumps, so-called oligomers. These oligomers are thought to be key players in the disease process. However, obtaining information about the exact , that is, the number of monomeric proteins that form one oligomer, remains very challenging, while this is essential information for understanding the disease process.

Single-molecule photobleaching and sub-stoichiometric labeling

The research team has developed a new method to determine the composition of these oligomers. Combining single-molecule photobleaching techniques with sub-stoichiometric fluorophore labeling gave insights into the number of monomers that form a protein oligomer. Single-molecule photobleaching uses ultrasensitive fluorescence microscopy to observe the successive photodestruction of fluorophores within one oligomer. To make this method suitable for large oligomers, the researchers have extended this method to be used in combination with sub-stoichiometric labeling, in which only a fraction of the monomeric proteins contain a fluorescent label, and statistical analysis of the data.

Alpha synuclein oligomers

The newly developed method can be applied in general to large macromolecular protein assemblies. The research team has focused on the neuronal alpha-synuclein, which plays a critical role in the onset and progression of Parkinson’s disease. They showed that alpha-synuclein oligomers prepared by a specific protocol are present as a single-well defined species consisting of 31 monomers per oligomer.

Explore further: Scientists identify most lethal known species of prion protein

More information: Full article: onlinelibrary.wiley.com/doi/10 … 2/anie.201200813/pdf

Related Stories

Scientists identify most lethal known species of prion protein

February 9, 2012
Scientists from the Florida campus of The Scripps Research Institute have identified a single prion protein that causes neuronal death similar to that seen in "mad cow" disease, but is at least 10 times more lethal than larger ...

SUMO defeats protein aggregates that typify Parkinson's disease

July 11, 2011
A small protein called SUMO might prevent the protein aggregations that typify Parkinson's disease (PD), according to a new study in the July 11, 2011, issue of The Journal of Cell Biology.

How Parkinson's disease starts and spreads

April 16, 2012
Injection of a small amount of clumped protein triggers a cascade of events leading to a Parkinson's-like disease in mice, according to an article published online this week in the Journal of Experimental Medicine.

Structure of Parkinson's disease protein identified

October 24, 2011
A team of researchers from the Petsko-Ringe and Pochapsky laboratories at Brandeis have produced and determined the structure of alpha-synuclein, a key protein associated with Parkinson’s disease.

Untangling the mysteries of Alzheimer's

February 2, 2012
One of the most distinctive signs of the development of Alzheimer's disease is a change in the behavior of a protein that neuroscientists call tau. In normal brains, tau is present in individual units essential to neuron ...

Recommended for you

Exosomes are the missing link to insulin resistance in diabetes

September 21, 2017
Chronic tissue inflammation resulting from obesity is an underlying cause of insulin resistance and type 2 diabetes. But the mechanism by which this occurs has remained cloaked, until now.

Thousands of new microbial communities identified in human body

September 20, 2017
A new study of the human microbiome—the trillions of microbial organisms that live on and within our bodies—has analyzed thousands of new measurements of microbial communities from the gut, skin, mouth, and vaginal microbiome, ...

Study finds immune system is critical to regeneration

September 20, 2017
The answer to regenerative medicine's most compelling question—why some organisms can regenerate major body parts such as hearts and limbs while others, such as humans, cannot—may lie with the body's innate immune system, ...

Immune cells produce wound healing factor, could lead to new IBD treatment

September 20, 2017
Specific immune cells have the ability to produce a healing factor that can promote wound repair in the intestine, a finding that could lead to new, potential therapeutic treatments for inflammatory bowel disease (IBD), according ...

As men's weight rises, sperm health may fall

September 20, 2017
(HealthDay)—A widening waistline may make for shrinking numbers of sperm, new research suggests.

New model may help science overcome the brain's fortress-like barrier

September 19, 2017
Scientists have helped provide a way to better understand how to enable drugs to enter the brain and how cancer cells make it past the blood brain barrier.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.