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Physics and biology team up to tackle protein folding debate

Lausanne, Switzerland A team of researchers from EPFL, (Ecole Polytechnique Fdrale 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 caf 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 mo
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Contact: Mary Parlange
mary.parlange@epfl.ch
41-21-693-7022
Ecole Polytechnique Fdrale de Lausanne
4-Apr-2006


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