Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New Interaction Mechanism of Proteins Discovered

22.02.2018

UZH researchers have discovered a previously unknown way in which proteins interact with one another and cells organize themselves. This new mechanism involves two fully unstructured proteins forming an ultra-high-affinity complex due to their opposite net charge. Proteins usually bind one another as a result of perfectly matching shapes in their three-dimensional structures.

Proteins are among the most important biomolecules and are the key mediators of molecular communication between and within cells. For two proteins to be able to bind, specific regions of their three-dimensional structure have to exactly match one another – like a key that fits into a lock.


Single molecule fluorescence spectroscopy makes the binding principle of unstructured proteins visible.

Christoph Schumacher, dunkelweiss

The structure of proteins is extremely important for their functioning and for triggering the required response in cells. Now researchers at the University of Zurich, together with colleagues from Denmark and the US, have discovered that unstructured proteins can also have ultra-high-affinity interactions.

Like boiled noodles in water

One of these proteins is histone H1, which as a component of chromatin is responsible for DNA packaging. Its binding partner, prothymosin α, acts as a kind of shuttle that deposits and removes the histone from the DNA. This process determines whether or not genes in specific parts of the DNA can be read. Both proteins are involved in several regulatory processes in the body, such as cell division and proliferation, and therefore also play a role when it comes to a number of diseases, e.g. cancer.

Ben Schuler, professor at the Department of Biochemistry at UZH and head of the research project published in Nature, explains: “The interesting thing about these proteins is that they’re completely unstructured – like boiled noodles in water.” How such disordered proteins should be able to interact according to the key/lock principle had puzzled the team of researchers.

Ultra-high-affinity despite lack of structure

What is remarkable is that the two proteins bind to one another much more strongly than the average protein partners. The research team used single-molecule fluorescence and nuclear magnetic resonance spectroscopy to determine the arrangement of the proteins. Observed in isolation, they show extended unstructured protein chains.

The chains become more compact as soon as both binding partners come together and form a complex. The strong interaction is caused by the strong electrostatic attraction, since histone H1 is highly positively charged while prothymosin α is highly negatively charged. Even more surprising was the discovery that the protein complex was also fully unstructured, as several analyses confirmed.

Unstructured, but highly dynamic complex

To investigate the shape of the protein complex, the researchers labeled both proteins with fluorescent probes, which they then added to selected sites on the proteins. Together with computer simulations, this molecular map yielded the following results: Histone 1 interacts with prothymosin α preferably in its central region, which is the region with the highest charge density. Moreover, it emerged that the complex is highly dynamic: The proteins’ position in the complex changes extremely quickly – in a matter of approx. 100 nanoseconds.

New interaction mechanism likely widespread

The interaction behavior discovered by the UZH researchers is likely to be fairly common. Living beings have many proteins that contain highly charged sequences and may be able to form such protein complexes. There are hundreds of such proteins in the human body alone. “It’s likely that the interaction between disordered highly charged proteins is a basic mechanism for how cells function and organize themselves,” concludes Ben Schuler.

According to the biophysicist, textbooks will need to be revised to account for this new way of binding. The discovery is also relevant for developing new therapies, since unstructured proteins are largely unresponsive to traditional drugs, which bind to specific structures on the protein surface.

Literature:
Alessandro Borgia, Madeleine B. Borgia, Katrine Bugge, Vera M. Kissling, Pétur O. Heidarsson, Catarina B. Fernandes, Andrea Sottini, Andrea Soranno, Karin J. Buholzer, Daniel Nettels, Birthe B. Kragelund, Robert B. Best, Benjamin Schuler. Extreme disorder in an ultra-high-affinity protein complex. Nature. 21 February 2018. DOI: 10.1038/nature25762

Contact:
Prof. Ben Schuler, PhD
Department of Biochemistry
University of Zurich
Phone +41 44 635 5535
E-mail: schuler@bioc.uzh.ch

Weitere Informationen:

http://www.media.uzh.ch/en/Press-Releases/2018/new-protein-interaction.html

Kurt Bodenmüller | Universität Zürich

More articles from Life Sciences:

nachricht Discovery of life in solid rock deep beneath sea may inspire new search for life on Mars
02.04.2020 | University of Tokyo

nachricht The architecture of a 'shape-shifting' norovirus
01.04.2020 | University of Leeds

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A sensational discovery: Traces of rainforests in West Antarctica

90 million-year-old forest soil provides unexpected evidence for exceptionally warm climate near the South Pole in the Cretaceous

An international team of researchers led by geoscientists from the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI) have now...

Im Focus: Blocking the Iron Transport Could Stop Tuberculosis

The bacteria that cause tuberculosis need iron to survive. Researchers at the University of Zurich have now solved the first detailed structure of the transport protein responsible for the iron supply. When the iron transport into the bacteria is inhibited, the pathogen can no longer grow. This opens novel ways to develop targeted tuberculosis drugs.

One of the most devastating pathogens that lives inside human cells is Mycobacterium tuberculosis, the bacillus that causes tuberculosis. According to the...

Im Focus: Physicist from Hannover Develops New Photon Source for Tap-proof Communication

An international team with the participation of Prof. Dr. Michael Kues from the Cluster of Excellence PhoenixD at Leibniz University Hannover has developed a new method for generating quantum-entangled photons in a spectral range of light that was previously inaccessible. The discovery can make the encryption of satellite-based communications much more secure in the future.

A 15-member research team from the UK, Germany and Japan has developed a new method for generating and detecting quantum-entangled photons at a wavelength of...

Im Focus: Junior scientists at the University of Rostock invent a funnel for light

Together with their colleagues from the University of Würzburg, physicists from the group of Professor Alexander Szameit at the University of Rostock have devised a “funnel” for photons. Their discovery was recently published in the renowned journal Science and holds great promise for novel ultra-sensitive detectors as well as innovative applications in telecommunications and information processing.

The quantum-optical properties of light and its interaction with matter has fascinated the Rostock professor Alexander Szameit since College.

Im Focus: Stem Cells and Nerves Interact in Tissue Regeneration and Cancer Progression

Researchers at the University of Zurich show that different stem cell populations are innervated in distinct ways. Innervation may therefore be crucial for proper tissue regeneration. They also demonstrate that cancer stem cells likewise establish contacts with nerves. Targeting tumour innervation could thus lead to new cancer therapies.

Stem cells can generate a variety of specific tissues and are increasingly used for clinical applications such as the replacement of bone or cartilage....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

13th AKL – International Laser Technology Congress: May 4–6, 2022 in Aachen – Laser Technology Live already this year!

02.04.2020 | Event News

“4th Hybrid Materials and Structures 2020” takes place over the internet

26.03.2020 | Event News

Most significant international Learning Analytics conference will take place – fully online

23.03.2020 | Event News

 
Latest News

Most of Earth's carbon was hidden in the core during its formative years

02.04.2020 | Earth Sciences

Discovery of life in solid rock deep beneath sea may inspire new search for life on Mars

02.04.2020 | Life Sciences

Geneticists are bringing personal medicine closer to recently admixed individuals

02.04.2020 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>