Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Floppy but fast

12.10.2015

Inside cells, communication between the nucleus, which harbours our precious genetic material, and the cytoplasm is mediated by the constant exchange of thousands of signalling molecules and proteins. Until now, it was unknown how this protein traffic can be so fast and yet precise enough to prevent the passage of unwanted molecules.

Through a combination of computer simulations and various experimental techniques, researchers from Germany, France and the UK have solved this puzzle. A very flexible and disordered protein can bind to its receptor within billionths of a second. Their research, led by Edward Lemke at EMBL, Frauke Gräter at the Heidelberg Institute for Theoretical Studies, and Martin Blackledge at Institut de Biologie Structurale, is published in Cell this week.


The ultrafast and yet selective binding allows the receptor (gold) to rapidly travel through the pore filled with disordered proteins (blue) into the nucleus, while any unwanted molecules are kept outside.

Credit: Mercadante /HITS

Proteins can recognize one another. Each engages very specifically with only a subset of the many different proteins present in the living cell, like a key slotting into a lock. But what if the key is completely flexible, as is the case for so-called intrinsically disordered proteins (IDPs)?

The research teams headed by Edward Lemke at EMBL Heidelberg, Frauke Gräter at the Heidelberg Institute for Theoretical Studies (HITS) and Martin Blackledge at the Institut de Biologie Structurale (IBS) in France, addressed this question in a highly interdisciplinary collaboration, combining molecular simulations, single molecule fluorescence resonance energy transfer (FRET), nuclear magnetic resonance (NMR), stopped flow spectroscopy and in-cell particle tracking.

Unexpectedly, they found that flexible, spaghetti-like proteins can be good - maybe even better than solid protein blocks - at being recognised by multiple partners. And they can do so very fast, while still retaining the high specificity the cell needs. In fact, this could be why these disordered molecules are more common in evolutionarily higher organisms, the researchers surmise.

Researchers had assumed that when an IDP 'key' needed to bind to its lock, it rearranged itself to become more rigid, but experiments in the Lemke lab hinted otherwise. "The pioneering single molecule experiments undertaken at EMBL showed for the particular interaction of a receptor with a disordered protein no hint of rigidity: the flexible protein stayed as flexible even when bound to its receptor" says Davide Mercadante (HITS).

This prompted him to study the very same interaction on the computer. The surprising result was that the high flexibility of the IDP actually helps it bind to its lock - in this case, a nuclear transport receptor, which shuttles proteins into the nucleus. The simulations even suggested the binding to be ultrafast - faster than any other association of that kind recorded to date.

"The computational data indicated that we might have identified a new ultrafast binding mechanism, but it took us three years to design experiments to prove the kinetics in the lab," Iker Valle Aramburu (EMBL) recalls. "In the end, we had a remarkably perfect match."

The results now help to understand a long-standing paradox: "For a cell to be viable, molecules must constantly move into and out of its nucleus", says Edward Lemke (EMBL). "Our findings explain the so-called transport paradox - that is, how this shuttling can be so very fast while remaining specific so that unwanted molecules cannot pass the barrier that protects our genome."

The new study suggests that many binding motifs at the surface of the IDP create a highly reactive surface that together with the very high speed of locking and unlocking ensures efficient proof-reading while the receptors to travel so fast through a pore filled with other IDPs.

"This is likely a new paradigm for the recognition of intrinsically disordered proteins." says Frauke Gräter (HITS). Since around 30-50% of the proteins in human cells are disordered, at least in some regions of the protein, the results may also provide a rationale for how recognition information can be processed very fast in general - which is vital to cells.

Other researchers involved in the study are working at the IBS in Grenoble, France, and Cambridge University, UK.

Media Contact

Sonia Furtado Neves
sonia.furtado@embl.de

 @EMBLorg

http://www.embl.org 

Sonia Furtado Neves | EurekAlert!

More articles from Life Sciences:

nachricht Molecular microscopy illuminates molecular motor motion
26.07.2017 | Penn State

nachricht New virus discovered in migratory bird in Rio Grande do Sul, Brazil
26.07.2017 | Fundação de Amparo à Pesquisa do Estado de São Paulo

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

 
Latest News

CCNY physicists master unexplored electron property

26.07.2017 | Physics and Astronomy

Molecular microscopy illuminates molecular motor motion

26.07.2017 | Life Sciences

Large-Mouthed Fish Was Top Predator After Mass Extinction

26.07.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>