Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

The structure of the BinAB toxin revealed: one small step for Man, a major problem for mosquitoes!

30.09.2016

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.


These crystals observed by electronic scanning microscopy (left) made it possible to elucidate the structure of the BinAB toxin (right). © Mari Gingery (left) / Jacques-Philippe Colletier (right).

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.

http://www.nature.com/nature/journal/vaop/ncurrent/full/nature19825.html

  • Full bibliographic informationDe novo phasing with X-ray laser reveals mosquito larvicide BinAB structure. Jacques-Philippe Colletier, Michael R. Sawaya, Mari Gingery, Jose A. Rodriguez, Duilio Cascio, Aaron S. Brewster, Tara Michels-Clark, Robert H. Hice, Nicolas Coquelle, Sébastien Boutet, Garth J. Williams, Marc Messerschmidt, Daniel P. DePonte, Raymond G. Sierra, Hartawan Laksmono, Jason E. Koglin, Mark S. Hunter, Hyun-Woo Park, Monarin Uervirojnangkoorn, Dennis K. Bideshi, Axel T. Brunger, Brian A. Federici, Nicholas K. Sauter, David S. Eisenberg. Nature, 28 septembre 2016. DOI: 10.1038/nature19825

Notes for editors

CNRS scientist l Jacques-Philippe Colletier l T +33 (0)4 57 42 85 15 l jacques-philippe.colletier@ibs.fr
CNRS press l Véronique Etienne l T +33 (0)1 44 96 51 51 l presse@cnrs.fr

Véronique Etienne | AlphaGalileo

Further reports about: CNRS Culex Nanocrystals X-ray malaria mosquito populations mosquitoes structure

More articles from Life Sciences:

nachricht More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>