Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Physics and biology team up to tackle protein folding debate


A team of researchers from EPFL, (Ecole Polytechnique Fédérale de Lausanne), the University of Lausanne, Northwestern University and Tel Aviv University bring biology and statistical physics together to answer the question of how molecular chaperones fold, unfold and pull proteins around in the cell. Their results appear the week of April 3 in the advance online edition of the Proceedings of the National Academy of Sciences.

A series of discussions in a campus café in Lausanne has blossomed into an extraordinary collaboration between EPFL physics professor Paolo De Los Rios and University of Lausanne biology professor Pierre Goloubinoff. Using the principles of statistical physics, they have identified a simple, single mechanism that explains the mechanical role of molecular chaperones in protein folding and translocation, settling at the same time a long-standing controversy over this process.

Molecular chaperones are specialized proteins that help other proteins find their proper conformations and reach their proper places in the cell. For more than two decades, biologists and biochemists have debated how one of these chaperones, Hsp70, manages the mechanical job of unfolding protein aggregates and pulling proteins into the various compartments of the cell. Is it by a “Power Stroke”, in which the chaperone would use leverage and produce a mechanical force that pulls the protein, or a “Brownian Ratchet”, in which the presence of the chaperone and the thermal fluctuations of the protein itself combine to pull the protein? There is no overwhelming evidence in favor of one explanation over the other. More importantly, neither theory explains the full range of Hsp70’s activity.

Using their prior results from biochemistry, De Los Rios and Goloubinoff turned to molecular geometry, statistical physics and the laws of thermodynamics in an attempt to solve the problem. The result, which they have dubbed “Entropic Pulling”, is a modified form of the Brownian Ratchet mechanism. Molecular systems, they explain, must obey the laws of physics and strive for equilibrium. In the process, they increase their entropy. When the Hsp70 molecule, attached to a protein, hits a membrane or an aggregate, a tiny force due to entropy pushes it away again, dragging the protein strand along with it. The collaborators demonstrated that this entropic effect, combined with the protein’s own thermal fluctuations, can exert enough force to pull a protein through the narrow pore of a mitochondrial membrane or disentangle an aggregate in the cell.

“Our explanation is so simple,” De Los Rios says, “that it almost seems disappointing. We have shown that all the functions of Hsp70 in the cell can be explained by one simple mechanism.”

Many diseases – among them mad cow, Parkinson’s and Alzheimer’s diseases -- are caused by misfolded proteins or aggregates. Goloubinoff emphasizes that understanding how chaperones such as Hsp70 function is important groundwork that must be laid before we can hope to develop strategies to treat these kinds of protein-misfolding pathologies.

Simple, elegant solutions often belie the struggle that went into their creation. The collaborators invested much time, energy (and coffee!) becoming familiar with the culture and language of each other’s discipline. Now the effort has borne fruit in an excellent demonstration of the potential of interdisciplinary research in physics and biology.

Mary Parlange | alfa
Further information:

More articles from Physics and Astronomy:

nachricht Sharpening the X-ray view of the nanocosm
23.03.2018 | Changchun Institute of Optics, Fine Mechanics and Physics

nachricht Drug or duplicate?
23.03.2018 | Fraunhofer-Institut für Angewandte Festkörperphysik IAF

All articles from Physics and Astronomy >>>

The most recent press releases about innovation >>>

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

Im Focus: Space observation with radar to secure Germany's space infrastructure

Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.

The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...

Im Focus: Researchers Discover New Anti-Cancer Protein

An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.

The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

New solar solutions for sustainable buildings and cities

23.03.2018 | Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

Latest News

For graphite pellets, just add elbow grease

23.03.2018 | Materials Sciences

Unique communication strategy discovered in stem cell pathway controlling plant growth

23.03.2018 | Agricultural and Forestry Science

Sharpening the X-ray view of the nanocosm

23.03.2018 | Physics and Astronomy

Science & Research
Overview of more VideoLinks >>>