Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Bacterial proteins: A structural switch leads to multifunctionality in gene expression

20.07.2012
In the current issue of the journal "Cell" an international group of researchers led by Prof. Paul Rösch at the Research Center for Bio-Macromolecules of the University of Bayreuth reports a surprising discovery combining the fields of bacterial genetics and structural biology.
The bacterial protein RfaH is able to adopt two completely different three-dimensional structures. Effected by external factors, the carboxyterminal domain switches from an all alpha helical to an all beta barrel conformation. This drastic conformational change enables the regulation of gene expression and protein translation by RfaH.

Nuclear magnetic resonance spectroscopy reveals the extraordinary structural switch of a protein

Proteins, basic molecular building blocks of life, consist of a chain of amino acids which usually adopts a unique three-dimensional structure dictated by the sequence of amino acids. Most proteins can fulfill specific functions only in a folded state. The traditional scientific view states that in a defined environment a certain protein can adopt only one distinct three-dimensional structure to accomplish its purpose.

Recent results from the Research Center for Bio-Macromolecules at the Universität Bayreuth evidenced that this view has to be modified: The protein RfaH from E. coli bacteria was studied in an international cooperation led by Prof. Paul Rösch. Using nuclear magnetic resonance spectroscopy, the researchers could show that the bacterial protein RfaH is able to adopt two completely different three-dimensional structures. Results of bacterial genetics studies demonstrate that the two structures accomplish entirely different functions. RfaH consists of two characteristic structural units, the aminoterminal domain (N-terminal domain, NTD) and the carboxyterminal domain (C-terminal domain, CTD), that are connected by a flexible linker. These domains are closely interacting and are thus in close proximity to each other. The CTD consists solely of two alpha helices (screw-like structures) in a hairpin arrangement. Binding of the NTD to a distinct piece of DNA leads to spatial separation of the domains, which in turn results in a complete structural switch of the CTD as it changes its structure from the alpha helical hairpin into a fold that completely differs from the starting structure (beta sheet).

In the closed form of RfaH (right), the C-terminal domain (CTD, blue) and the N-terminal domain (NTD, green) are close to each other. The alpha-helical CTD masks the area of the NTD which binds to the RNA polymerase. Binding to a specific piece of DNA results in domain separation (left) which in turn leads to the complete refolding of the CTD. In this state, the NTD can bind RNA polymerase and the CTD can bind ribosomal protein S10. RfaH is thus a regulatory component of the transcription of DNA into RNA.

Image: Dr. Stefan Knauer, University of Bayreuth; free for publication only when reference is included.

"Never before has such a fundamental structural change been observed for proteins", Prof. Paul Rösch notes. "This result is spectacular as we were able to simultaneously elucidate the structural transition and its functional consequences for central cellular processes in bacteria." RfaH's ability to change its structure enables regulation of the translation of bacterial genetic information into proteins (gene expression).

Regulatory functions of the domains in gene expression

Gene expression starts with the transcription of the genetic information contained in DNA into RNA. The molecular machine for this process is RNA polymerase. Transcription is followed by the production of new proteins based on RNA (translation) at a different cellular component, the ribosome.

Its ability to change its structure allows RfaH to physically couple the main actors of these processes. After domain dissociation, the NTD of the protein binds to RNA polymerase, while the refolded CTD interacts with the ribosome. This binding is mediated by the protein S10 that is part of the ribosome. The spectacular structural switch of RfaH enables the protein to couple transcription and translation by bridging the two principal components, RNA polymerase and ribosome. The option of a regulated domain separation and the resulting complete refolding of the CTD explains the central role of the protein RfaH in the modulation of bacterial gene expression on the level of molecular structures.

The partner proteins RfaH and NusG

Why does RfaH exist in a non-functional state at all? Studies of the protein NusG provided hints to an answer. NusG like RfaH consists of an NTD and a CTD, but the two domains are always separated, and the CTD exists in beta sheet structure only. The NTD of NusG also binds to RNA polymerase and the CTD to the ribosome via S10. However, NusG is a protein that is generally involved in bacterial gene expression while, in contrast, RfaH is employed only in very specialized transcription events. To ensure that RfaH does not interfere with NusG, the alpha helical CTD of RfaH masks precisely the area of the NTD which could interact with RNA polymerase. Also, the CTD in its alpha helical state is not able to bind to the ribosome. Thus, RfaH is inhibited in both functions. The protein is activated by domain separation and refolding of the CTD to beta sheet structure – only then the two domains can bind their partners.

International cooperation

These results published in "Cell" are the outcome of a long-standing transatlantic cooperation. The Research Center for Bio-Macromolecules (BIOmac) at the Universität Bayreuth led by Prof. Paul Rösch has cooperated closely with biochemists, bacteriologists, and microbiologists of Ohio State University and of the University of Wisconsin. The Deutsche Forschungsgemeinschaft (DFG) in Germany and the National Institutes of Health (NIH) in the USA supported the research.

Outlook

"Together we discovered an example of how a protein can change its fold fundamentally to be able to fulfill different functions", Prof. Paul Rösch explains. "The principle of making proteins multifunctional by switching their three-dimensional structure is so strikingly simple that we are prepared to find similar mechanisms in other molecular processes."

Publication:

Burmann et al., An α Helix to β Barrel Domain Switch Transforms the Transcription Factor RfaH into a Translation Factor,
Cell (2012), http://dx.doi.org/10.1016/j.cell.2012.05.042

Svetlov and Nudler, Unfolding the Bridge between Transcription and Translation,
Cell (2012), http://dx.doi.org/10.1016/j.cell.2012.06.025

Burmann et al., A NusE:NusG Complex Links Transcription and Translation.
Science. 2010 328:501-4.

Video:

An explanatory video can be found at http://www.cell.com

Contact:

Prof. Dr. Paul Rösch
Forschungszentrum für Bio-Makromoleküle
Universität Bayreuth
D-95440 Bayreuth
Tel. +49 (0)921 55-3540
E-Mail: roesch@unibt.de

Christian Wißler | Universität Bayreuth
Further information:
http://www.uni-bayreuth.de

More articles from Life Sciences:

nachricht Helping to Transport Proteins Inside the Cell
21.11.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht UNH researchers create a more effective hydrogel for healing wounds
21.11.2018 | University of New Hampshire

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First diode for magnetic fields

Innsbruck quantum physicists have constructed a diode for magnetic fields and then tested it in the laboratory. The device, developed by the research groups led by the theorist Oriol Romero-Isart and the experimental physicist Gerhard Kirchmair, could open up a number of new applications.

Electric diodes are essential electronic components that conduct electricity in one direction but prevent conduction in the opposite one. They are found at the...

Im Focus: Nonstop Tranport of Cargo in Nanomachines

Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.

Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...

Im Focus: UNH scientists help provide first-ever views of elusive energy explosion

Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.

Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...

Im Focus: A Chip with Blood Vessels

Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.

Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...

Im Focus: A Leap Into Quantum Technology

Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.

In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Optical Coherence Tomography: German-Japanese Research Alliance hosted Medical Imaging Conference

19.11.2018 | Event News

“3rd Conference on Laser Polishing – LaP 2018” Attracts International Experts and Users

09.11.2018 | Event News

On the brain’s ability to find the right direction

06.11.2018 | Event News

 
Latest News

Helping to Transport Proteins Inside the Cell

21.11.2018 | Life Sciences

Meta-surface corrects for chromatic aberrations across all kinds of lenses

21.11.2018 | Power and Electrical Engineering

Removing toxic mercury from contaminated water

21.11.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>