New insights into energy generation by heat shock protein Hsp90
Many enzymes work only with a co-trainer, of sorts. Scientists at the Technische Universitaet Muenchen (TUM) and the Cluster of Excellence Nanosystems Initiative Munich (NIM) show what this kind of cooperation looks like in detail using a novel methodology applied to the heat shock protein Hsp90.
As in a successful football match, all actors in a cell must play in perfect coordination. A typical example for this kind of cooperation can be seen in the heat shock protein Hsp90, which controls the proper folding of other proteins. Together with a second molecule, the co-chaperone P23, it splits the energy source ATP to yield the energy it needs to do its work.
However, while normal enzyme reactions often are easy to follow because the involved proteins alter their conformations clearly, the interaction between P23 and ATP involves significantly less conspicuous changes in state.
Using a sophisticated methodology, a team led by Professor Thorsten Hugel, head of the Research Group for Molecular Machines at the TU München and member of the Cluster of Excellence Nanosystems Initiative Munich (NIM), has now managed to observe this reaction in detail for the first time – step for step with single molecules of Hsp90, P23 and ATP.
Live transmission of molecular processes
To this end, the team adapted the so-called FRET (Foerster resonance energy transfer) methodology to suit their requirements. The approach works by using a variety of fluorescent dye molecules bonded to specific sites in the involved components. When these complexes are excited with light of a specific wavelength, the pigments start to fluoresce in a kind of chain reaction. The emitted fluorescent light reveals the precise distance between the marked sites, right down to the nanometer.
To determine exactly how the components Hsp90, P23 and ATP interact with each other, the biophysicists observed the positions and bonding sequences of the individual molecules over a span of several minutes. From the resulting data they could deduce even the smallest of changes, as well as the biological function of the overall complex.
Energy production only as a team
Using this approach, the Munich researchers successfully demonstrated in detail that the P23 protein strengthens ATP bonding, thereby significantly increasing the amount of energy exploited. They also showed that the two substances bond with Hsp90 this effectively only as a team, thereby allowing ATP splitting to be used so successful.
“Without P23 the heat shock enzyme effectively runs on idle,” explains Bjoern Hellenkamp the results. “When P23 joins the game, it is like shifting into gear. The energy is released and the reaction moves clearly in one direction. This is referred to as directionality.”
In the near future the biophysicists want to investigate in detail how Hsp90 uses the exploited energy. The newly established methodology also allows them to investigate other multicomponent systems with mechanisms that have eluded study because of their minimal conformational alterations.
Four-colour FRET reveals directionality in the Hsp90 multicomponent machinery
C. Ratzke, B. Hellenkamp, T. Hugel
Nature Communications 5, Article number: 4192. Published online: 20 June 2014
Andreas Battenberg | Technische Universität München
Shark Tagged by NSU’s Guy Harvey Research Institute Is Apparently Enjoying Time in Warm, Tropical Waters
30.03.2015 | Nova Southeastern University
Misuse of Sustainability Concept May Lead to Even More Toxic Chemical Materials
30.03.2015 | Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences
In an experiment at the Department of Energy's SLAC National Accelerator Laboratory, scientists precisely measured the temperature and structure of aluminum as...
The IPH presents a solution at HANNOVER MESSE 2015 to make ship traffic more reliable while decreasing the maintenance costs at the same time. In cooperation with project partners, the research institute from Hannover, Germany, has developed a sensor system which continuously monitors the condition of the marine gearbox, thus preventing breakdowns. Special feature: the monitoring system works wirelessly and energy-autonomously. The required electrical power is generated where it is needed – directly at the sensor.
As well as cars need to be certified regularly (in Germany by the TÜV – Technical Inspection Association), ships need to be inspected – if the powertrain stops...
When an earthquake hits, the faster first responders can get to an impacted area, the more likely infrastructure--and lives--can be saved.
The Atlantic overturning is one of Earth’s most important heat transport systems, pumping warm water northwards and cold water southwards. Also known as the Gulf Stream system, it is responsible for the mild climate in northwestern Europe.
Scientists now found evidence for a slowdown of the overturning – multiple lines of observation suggest that in recent decades, the current system has been...
Because they are regularly subjected to heavy vehicle traffic, emissions, moisture and salt, above- and underground parking garages, as well as bridges, frequently experience large areas of corrosion. Most inspection systems to date have only been capable of inspecting smaller surface areas.
From April 13 to April 17 at the Hannover Messe (hall 2, exhibit booth C16), engineers from the Fraunhofer Institute for Nondestructive Testing IZFP will be...
25.03.2015 | Event News
19.03.2015 | Event News
17.03.2015 | Event News
30.03.2015 | Press release
30.03.2015 | Life Sciences
30.03.2015 | Earth Sciences