Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Biophysicists manipulate 'zipper,' reveal protein folding dynamics

19.01.2010
Single-molecule, real-time measurements of a key biological process

Biophysicists at TUM, the Technische Universitaet Muenchen, have published the results of single-molecule experiments that bring a higher-resolution tool to the study of protein folding.

How proteins arrive at the three-dimensional shapes that determine their essential functions – or cause grave diseases when folding goes wrong – is considered one of the most important and least understood questions in the biological and medical sciences.

Folding itself follows a path determined by its energy landscape, a complex property described in unprecedented detail by the TUM researchers. In this week's issue of the Proceedings of the National Academy of Sciences (USA), they report taking hold of a single, zipper-like protein molecule and mapping changes in its energy landscape during folding and unfolding.

Previous studies, including atomic force microscopy experiments by the same Munich laboratory, have gone a long way toward characterizing energy thresholds or barriers that stand between a protein's unfolded and folded states. Detailed observations of the quick transition from one state to the other have remained elusive. The results published this week open the door to higher-resolution, direct measurements. Better characterization of the folding process is seen as a vital link in understanding the chain of events leading from DNA coding for a protein to that protein's biological function. Another motivation for research in this field is the search for new drugs and therapies, because malfunctions in protein folding are implicated in a number of serious diseases – including diabetes, cancer, cystic fibrosis, prion diseases, and Alzheimer's.

This is the latest in a long series of single-molecule biophysical experiments carried out by Professor Matthias Rief and colleagues in the TUM Department of Physics. Co-authors Christof Gebhardt and Thomas Bornschloegl are members of Rief's lab; Gebhardt also is a member of the Munich Center for Integrated Protein Science.

As a model system for studying real-time protein folding dynamics, the TUM scientists chose a so-called leucine zipper found in yeast. It offers, as proteins go, a relatively simple "coiled coil" structure and zipper-like folding action: Picture two amino acid strings side by side, joined at the bottom, open at the top, and made essentially to zip together.

The researchers extended this structure so that they could make independent measurements at the top, bottom, and middle parts of the zipper. They took hold of the free ends at the top of the zipper with handles made of double-stranded DNA. These DNA handles in turn were attached to tiny beads that could be directly manipulated by "optical tweezers" – a tool based on the ability of laser beams with a certain kind of profile to pin down nanoscale objects. One end of the protein molecule was held fixed, and the other was held under tension but with some freedom to move, so that folding dynamics could be measured directly, in real time, as the protein zipped and unzipped. This arrangement enabled measurements with high resolution in both space and time.

"What I consider the major improvement is that the new experiments allow the observation of thousands of transitions between the folded and the unfolded state," Rief said. "This enables us to detect not only the folded and unfolded states but also, directly, the excursions of the large energy barriers separating those states. This has previously been impossible, and it now allows direct insight into the precise energy profile of this barrier."

Publication: Full distance resolved folding energy landscape of one single protein molecule, by J. Christof M. Gebhart, Thomas Bornschloegl, and Matthias Rief, PNAS Early Edition for the week of Jan. 18, 2010.

Contact:

Prof. Matthias Rief
Chair for Experimental Physics
Technische Universität Muenchen (TUM)
James-Franck-Str. 1
85748 Garching, Germany
Tel: +49 89 289 12471
Fax: +49 89 289 12523
E-mail: mrief@ph.tum.de

Patrick Regan | EurekAlert!
Further information:
http://portal.mytum.de

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>