Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Similarities cause protein misfolding

31.05.2011
A large number of illnesses stem from misfolded proteins, molecules composed of amino acids. Researchers at the University of Zurich have now studied protein misfolding using a special spectroscopic technique. Misfolding, as they report in Nature, is more frequent if the sequence of the amino acids in the neighboring protein domains is very similar.

Proteins are the main molecular machines in our bodies. They perform a wide range of functions, from digesting and processing nutrients, converting energy and aiding cell structure to transmitting signals in cells and the whole body. In order to perform these highly specific functions, proteins have to adopt a well-defined, three-dimensional structure. Remarkably, in most cases they find this structure unaided once they have been formed out of their individual building blocks, amino acids, as a long chain molecule in the cell.

However, the process of protein folding can also go wrong, which means the proteins affected are no longer able to perform their function. In some cases, this can even have much more serious consequences if these misfolded proteins clump and trigger neurodegenerative diseases such as Alzheimer’s or Parkinson’s disease.

In the course of evolution, a crucial factor in the development of proteins has thus been to avoid such “misfolding processes”. However, this is no easy task since the same molecular interactions that stabilize the correct structure of the individual proteins can also bring about interactions between protein molecules, causing them to misfold.

Using a special spectroscopic method called single-molecule fluorescence, researchers from the Universities of Zurich and Cambridge have now studied the circumstances under which misfolding occurs. The team headed by Prof. Benjamin Schuler from the University of Zurich studied sections, or “domains”, of the largest protein in our bodies, titin, which helps the stability and elasticity of the muscle fibers. It is assumed that individual titin domains can unfold while the muscle is heavily exerted to avoid damaging the muscle tissue. When the muscle relaxes again, however, there is a danger that these unfolded domains might fold incorrectly. There is also a similar risk for other multidomain proteins.

For their study, the researchers attached small dye molecules as probes in the protein. “Using our laser-spectroscopic method we were able to determine distances on a molecular scale, i.e. down to a few millionths of a millimeter, through the energy transfer between the probes,” explains Prof. Schuler. This enabled the structures of correctly and misfolded proteins to be distinguished and thus the proportion of misfolding determined.

“The study of different titin domains in our experiments revealed that the probability of misfolding increases if neighboring domains are very similar in the sequence of their amino acids,” says Prof. Schuler. This is apparently the reason why neighboring domains in proteins have a limited degree of similarity. “This seems to be a key evolutionary strategy to avoid protein misfolding and thus guarantee their maximum functionality,” says Schuler.

Literature:
Borgia Madeleine B., Borgia Alessandro, Best Robert B., Steward Annette, Nettels Daniel, Wunderlich Bengt, Schuler Benjamin & Clarke Jane: Single-molecule fluorescence reveals sequence-specific misfolding in multidomain proteins, in: Nature, doi:10.1038/nature10099.
Contact:
Prof. Benjamin Schuler
Institute of Biochemistry
University of Zurich
Tel.: +41 44 63 55535
E-Mail: schuler@bioc.uzh.ch
www.bioc.uzh.ch

Beat Müller | Universität Zürich
Further information:
http://www.bioc.uzh.ch
http://www.mediadesk.uzh.ch

More articles from Life Sciences:

nachricht Nesting aids make agricultural fields attractive for bees
20.07.2017 | Julius-Maximilians-Universität Würzburg

nachricht The Kitchen Sponge – Breeding Ground for Germs
20.07.2017 | Hochschule Furtwangen

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

Leipzig HTP-Forum discusses "hydrothermal processes" as a key technology for a biobased economy

12.07.2017 | Event News

 
Latest News

Researchers create new technique for manipulating polarization of terahertz radiation

20.07.2017 | Information Technology

High-tech sensing illuminates concrete stress testing

20.07.2017 | Materials Sciences

First direct observation and measurement of ultra-fast moving vortices in superconductors

20.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>