The worldwide spreading of the whooping cough, also known as pertussis, has substantially increased since 2010. Researchers from the Biozentrum, University of Basel, have investigated structure and function of an important membrane protein of the bacterium causing pertussis. They discovered that the protein structure differs from a previously postulated model. Their findings, published in “Nature Communications”, provide a basis for new treatment approaches for the infection.
Many tiny protein pores are found in the outer membrane of the pertussis pathogen, the bacterium Bordetella pertussis. Through these pores, the pathogen secretes proteins, which are important for bacterial attachment in the human respiratory tract and for the formation of resistant biofilms.
In order to understand how membrane pores allow passage of their substrates, the structural biologists Prof. Timm Maier und Prof. Sebastian Hiller from the Biozentrum of the University of Basel, have taken a closer look at one of these proteins.
Membrane protein structure different than expected
Cellular membranes are barriers, which protect the cell from the outside world. Certain molecules can however still move across these barriers at specifically designed sites. The membrane protein FhaC in the pertussis pathogen is such a border guard. It is located on the outer cell membrane and channels the adhesin FHA across the membrane to the outside. FHA allows the bacterium to attach to host surfaces and thus plays an important role in the pertussis infection.
In 2007, the structure and function of FhaC had been published in Science. In the light of the new study, those findings have now been partly revised. “On the basis of our data, we have concluded that the previously postulated structure and mode of action of the FhaC protein required revision”, says Maier. Together with the authors of the original article, the researchers at the Biozentrum have now corrected the FhaC model.
“In contrast to earlier assumptions, our investigations have shown that the FhaC protein has the same architecture as proteins that integrate new membrane proteins”, explains Maier. The structural analysis also revealed how a helical protein domain acts like a plug, closing the pore in the absence of a cognate substrate. When the FHA adhesin binds to the membrane protein FhaC, this plug is released, the pore opens and the adhesion traverses the membrane.
A basis for new pertussis treatments
Pertussis disease is well controlled in Switzerland, but nonetheless, its occurrence is increasing since 2010. This calls for new treatment approaches. “Targeted inhibitors could significantly impair the FhaC function to prevent the pathogen from attaching to the host cell”, explains Maier. “The advantage is obvious: Antibiotic use can be avoided thus preventing the development of resistance.” The structural biologists aim to provide further fundamental insights in the future. Their plan is to investigate the role of individual protein components in the overall process of substrate channeling.
Timm Maier, Bernard Clantin, Fabian Gruss, Frédérique Dewitte, Anne-Sophie Delattre, Françoise Jacob-Dubuisson, Sebastian Hiller & Vincent Villeret
Conserved Omp85 lid-lock structure and substrate recognition in FhaC
Nature Communications; published online 10 June 2015, doi: 10.1038/ncomms8452
Prof. Timm Maier, University of Basel, Biozentrum, phone: +41 61 267 21 76, email: firstname.lastname@example.org
Katrin Bühler | Universität Basel
Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Life Sciences
27.04.2017 | Physics and Astronomy
27.04.2017 | Earth Sciences