Shining light on amyloid protein nanostructures

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.

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

Related Stories

Research reveals early steps in Parkinson's pathology

Apr 06, 2010

Although the cause of Parkinson's disease remains a mystery, scientists now have a better understanding of the earliest stages of abnormal aggregation of a key disease-associated protein. The research, published by Cell Press ...

How Parkinson's disease starts and spreads

Apr 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

Oct 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.

Recommended for you

A hybrid vehicle that delivers DNA

23 hours ago

A new hybrid vehicle is under development. Its performance isn't measured by the distance it travels, but rather the delivery of its cargo: vaccines that contain genetically engineered DNA to fight HIV, cancer, ...

User 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.