Could we get rid of mosquitoes without polluting the environment? Yes, we can! The BinAB toxin, produced in crystal form by a bacterium, specifically kills the larvae of Culex and Anopheles mosquitoes, but it is inactive on tiger mosquitoes (or Aedes), the vectors for dengue fever and chikungunya. Knowledge of the molecular structure of BinAB is necessary if we are to broaden its spectrum of action. Having long been inaccessible, this structure is now being published on 28 September 2016 in Nature by an international consortium involving scientists from the Institut de Biologie Structurale (CNRS/CEA/Université Grenoble Alpes) in France, and UCLA, UCR and SLAC in the USA.
Mosquitoes are vectors for numerous devastating diseases, including malaria that is spread by Anopheles mosquitoes, and filariasis transmitted by Culex mosquitoes. The BinAB toxin, produced in the form of nanocrystals by the bacterium Bacillus sphaericus, specifically targets the larvae of these two groups of mosquitoes.
A complex, five-step intoxication process (see insert, below) explains the environmental safety of BinAB, which is harmless to other insects, crustaceans and humans. BinAB is therefore used in many countries to regulate mosquito populations.
Unfortunately, the strength of BinAB is also its weakness: the toxin is ineffective on the larvae of Aedes mosquitoes, which spread the viruses for Dengue, Zika and chikungunya. A remodeling of BinAB might allow a broadening of its spectrum, but to achieve this it is necessary to understand its structure.
X-ray crystallography is an excellent method to reveal the structure of a protein, but it is generally only applicable to large crystals measuring around a tenth of a millimeter. Yet, the nanocrystals of BinAB that develop in vivo only measure ten-thousandths of a millimeter, and once dissolved, the toxin does not recrystallize.
An international consortium of scientists led by Jacques-Philippe Colletier, CNRS scientist at the Institut de Biologie Structurale (CNRS/CEA/Université Grenoble Alpes), Brian Federici, Professor at the University of California, Riverside (UCR) and David Eisenberg, Professor at the University of California, Los Angeles (UCLA), has just published this structure, solved by working on natural nanocrystals.
Faced with the obstacle of the small size of these crystals, they employed a new type of X-ray source, a free-electron laser, delivering ultra-short but highly intense X-ray pulses. Because nothing was known of the structure of BinAB, a purely experimental approach for structure determination (de novo phasing) was required, which had previously only been applied to samples of known structures in order to demonstrate its feasibility.
Thus the structure of BinAB is not only the first to have been solved from such small crystals (~ 300 nm) but also the first unknown structure to have been revealed de novo using a free-electron laser. This raises hopes of solving structures from smaller and more complex natural assemblages, such as organelles, the constituents of cells.
More immediately, understanding the structure of BinAB opens the way towards broadening its spectrum of action, with the aim to develop a “three-in-one” toxin that can target the larvae of three types of mosquito: Aedes (in order notably to control the spread of Zika virus), Culex (the vector for filariasis) and Anopheles (the vector for malaria).
The functioning of BinAB for the regulation of mosquito populations
The BinAB toxin is produced in the form of nanocrystals by Bacillus sphaericus bacteria at sporulation, or in other words when its nutrient resources diminish. Possibly attracted by the crystal, the mosquito larva eats the spore. The crystal dissolves in the larval gut where the pH is very high, releasing the BinAB toxin in a soluble form. BinAB is a binary toxin comprising two proteins, one of which specifically targets a receptor on the surface of intestinal cells (BinB), while the other serves exclusively to kill the cells (BinA). After dissolution of the crystal, BinA remains associated with BinB and the two partners are activated by the (enzymatic) digestion of their extremities (propeptides). BinB then binds to its receptor and assists the internalization of BinA – an essential step so that it can trigger the formation of a pore and thus kill the cell from the inside. What is the trophy for the bacterium? A larder where it can reproduce and survive.
Notes for editors
CNRS scientist l Jacques-Philippe Colletier l T +33 (0)4 57 42 85 15 l email@example.com
CNRS press l Véronique Etienne l T +33 (0)1 44 96 51 51 l firstname.lastname@example.org
Véronique Etienne | AlphaGalileo
Symbiotic bacteria: from hitchhiker to beetle bodyguard
28.04.2017 | Johannes Gutenberg-Universität Mainz
Nose2Brain – Better Therapy for Multiple Sclerosis
28.04.2017 | Fraunhofer-Institut für Grenzflächen- und Bioverfahrenstechnik IGB
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...
28.04.2017 | Event News
20.04.2017 | Event News
18.04.2017 | Event News
28.04.2017 | Medical Engineering
28.04.2017 | Earth Sciences
28.04.2017 | Life Sciences