Energy-saving chaperon Hsp90

Jan 13, 2012
With their specially designed three-color single-molecule FRET (Foerster resonance energy transfer) assay with alternating laser excitation (ALEX) for simultaneous observation of ATP binding and conformational changes professor Hugel and his team could prov, that Hsp90 utilizes thermal fluctuations for its large conformational changes. Credit: Christoph Ratzke

A special group of proteins, the so-called chaperons, helps other proteins to obtain their correct conformation. Until now scientists supposed that hydrolyzing ATP provides the energy for the large conformational changes of chaperon Hsp90. Now a research team from the Nanosystems Initiative Munich could prove that Hsp90 utilizes thermal fluctuations as the driving force for its conformational changes. The renowned journal PNAS reports on their findings.

ATP is the major energy source for most organisms and ATPases are the machines, which utilize this fuel, for example to move muscles or cargo in our body. The very abundant Hsp90 has such an ATPase in each of its two . During the last years experiments had suggested that the movement and conformational changes of ATPase proteins are in general strictly linked to ATP binding and hydrolysis (i.e. ).

To probe this theory Thorsten Hugel, Professor at the Technische Universitaet Muenchen (TUM) and member of the Nanosystems Initiative Munich (NIM), and his team designed a special three color single-molecule FRET (Förster resonance energy transfer) assay with alternating laser excitation (ALEX) for simultaneous observation of ATP binding and conformational changes. Unexpectedly the experiments revealed that binding and hydrolysis of ATP is not correlated with the large conformational changes of Hsp90. Hsp90 is instead a highly flexible machinery driven by .

"Thermal fluctuations are random changes in the structure of the – they can be thought of as collisions with water molecules in the environment, which move rather violently at the temperatures in a living organism," says Thorsten Hugel. "Using these clashes to switch back and forth between different conformations, saves Hsp90 valuable ATP." But then what is the task of ATPase in the Hsp90 chaperone? The scientists suspect that co-chaperones and substrate proteins alter the system so that ATP binding or can take a crucial task.

With the newly developed experimental setup, it is now possible to investigate the very complex system in greater detail to resolve this important question. The Munich biophysicists therewith offer a new perspective on the energy conversion in molecular machines.

Explore further: Discovery reveals how bacteria distinguish harmful versus helpful viruses

More information: PNAS, January 3, 2012 vol. 109, no. 1, 161-166 – Doi: 10.1073/pnas.1107930108

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C_elegans
not rated yet Jan 13, 2012
I'm so confused, I thought Hsp90 required ATP for in vitro functionality? These assays do not use co-chaperones, and also do not function when non-hydrolyzable ATP analogues (AP-PNP) are used. How are proteins released and reset to their receptive conformation without the release of ATP? If indeed, ATP is not required for Hsp90 function, then why did the authors not demonstrate substrate refolding in the presence of an ATP analogue? The authors claim that ATP may be used for "processing of substrates", isn't this THE crucial function of Hsp90? Please, I need a biochemist to dumb this down for me.