Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Physics and biology team up to tackle protein folding debate

05.04.2006


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:
http://www.epfl.ch

More articles from Physics and Astronomy:

nachricht MSU astronomers discovered supermassive black hole in an ultracompact dwarf galaxy
14.08.2018 | Lomonosov Moscow State University

nachricht ASU astrophysicist helps discover that ultrahot planets have starlike atmospheres
13.08.2018 | Arizona State University

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: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

Im Focus: Lining up surprising behaviors of superconductor with one of the world's strongest magnets

Scientists have discovered that the electrical resistance of a copper-oxide compound depends on the magnetic field in a very unusual way -- a finding that could help direct the search for materials that can perfectly conduct electricity at room temperatur

What happens when really powerful magnets--capable of producing magnetic fields nearly two million times stronger than Earth's--are applied to materials that...

Im Focus: World record: Fastest 3-D tomographic images at BESSY II

The quality of materials often depends on the manufacturing process. In casting and welding, for example, the rate at which melts solidify and the resulting microstructure of the alloy is important. With metallic foams as well, it depends on exactly how the foaming process takes place. To understand these processes fully requires fast sensing capability. The fastest 3D tomographic images to date have now been achieved at the BESSY II X-ray source operated by the Helmholtz-Zentrum Berlin.

Dr. Francisco Garcia-Moreno and his team have designed a turntable that rotates ultra-stably about its axis at a constant rotational speed. This really depends...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

2018 Work Research Conference

25.07.2018 | Event News

 
Latest News

'Building up' stretchable electronics to be as multipurpose as your smartphone

14.08.2018 | Information Technology

During HIV infection, antibody can block B cells from fighting pathogens

14.08.2018 | Life Sciences

First study on physical properties of giant cancer cells may inform new treatments

14.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>