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
More than just a mechanical barrier – epithelial cells actively combat the flu virus
04.05.2016 | Helmholtz-Zentrum für Infektionsforschung
Discovery of a fundamental limit to the evolution of the genetic code
03.05.2016 | Institute for Research in Biomedicine (IRB Barcelona)
Using an ultra fast-scanning atomic force microscope, a team of researchers from the University of Basel has filmed “living” nuclear pore complexes at work for the first time. Nuclear pores are molecular machines that control the traffic entering or exiting the cell nucleus. In their article published in Nature Nanotechnology, the researchers explain how the passage of unwanted molecules is prevented by rapidly moving molecular “tentacles” inside the pore.
Using high-speed AFM, Roderick Lim, Argovia Professor at the Biozentrum and the Swiss Nanoscience Institute of the University of Basel, has not only directly...
If a person pushes a broken-down car alone, there is a certain effect. If another person helps, the result is the sum of their efforts. If two micro-particles are pushing another microparticle, however, the resulting effect may not necessarily be the sum their efforts. A recent study published in Nature Communications, measured this odd effect that scientists call “many body.”
In the microscopic world, where the modern miniaturized machines at the new frontiers of technology operate, as long as we are in the presence of two...
Researchers from the Max Planck Institute Stuttgart have developed self-propelled tiny ‘microbots’ that can remove lead or organic pollution from contaminated water.
Working with colleagues in Barcelona and Singapore, Samuel Sánchez’s group used graphene oxide to make their microscale motors, which are able to adsorb lead...
Neutron scattering and computational modeling have revealed unique and unexpected behavior of water molecules under extreme confinement that is unmatched by any known gas, liquid or solid states.
In a paper published in Physical Review Letters, researchers at the Department of Energy's Oak Ridge National Laboratory describe a new tunneling state of...
Honeycomb structures as the basic building block for industrial applications presented using holo pyramid
Researchers of the Alfred Wegener Institute (AWI) will introduce their latest developments in the field of bionic lightweight design at Hannover Messe from 25...
27.04.2016 | Event News
15.04.2016 | Event News
12.04.2016 | Event News
04.05.2016 | Physics and Astronomy
04.05.2016 | Physics and Astronomy
04.05.2016 | Materials Sciences