Large conformational changes without ATP consummation
Energy saving chaperone Hsp90
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 chaperone protein Hsp90 has such an ATPase in each of its two monomers. 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. fuel consumption).
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.
"Thermal fluctuations are random changes in the structure of the protein – 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 cochaperones and substrate proteins alter the system so that ATP binding or hydrolysis 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.
Original publication
Other news from the department science
Get the life science industry in your inbox
From now on, don't miss a thing: Our newsletter for biotechnology, pharma and life sciences brings you up to date every Tuesday and Thursday. The latest industry news, product highlights and innovations - compact and easy to understand in your inbox. Researched by us so you don't have to.