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 The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | 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: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>