MENLO PARK, Calif., Sept. 28 (UPI) -- The toxin BinAB is currently used to combat malaria, West Nile virus and viral encephalitis. The toxin features insecticidal protein crystals, which are deadly when ingested by mosquito larvae.
Unfortunately, the toxin isn't effective against the mosquitoes that carry dengue fever and the Zika virus, but scientists are trying to change that. To do so, they've recruited the help of the U.S. Department of Energy's X-ray free-electron laser, the Linac Coherent Light Source.
Though BinAB is widely used, scientists have until recently remained in the dark on the mechanisms of its toxicity.
In a series of recent tests, LCLS helped researchers image and analyze the structure of the toxin's tiny protein crystals, revealing the sources of its potency.
"A more detailed look at the proteins' structure provides information fundamental to understanding how the crystals kill mosquito larvae," researcher Jacques-Philippe Colletier, a scientist at the Institut de Biologie Structurale in France, said in a news release. "This is a prerequisite for modifying the toxin to adapt it to our needs."
Colletier is the lead author of a new paper on BinAB's potential use in fight against Zika, published this week in the journal Nature.
BinAB doesn't work on contact, it must be ingested and exposed to the alkaline environs of the larva's gut. Upon exposure, the crystals forming the binary protein dissolve and its toxicity is activated.
Previous research has shown protein B to be essential to consumption. It sneaks A into the gut and helps it attach to the intestine. Once inside, A kills the larva.
Researchers used a special imaging technique to reveal the deadly magic of the protein crystals. Scientists tagged the binary protein with heavy metal markers, and then used the X-ray free-electron laser to track the movement of the markers.
"This is the first time we've used de novo phasing on a crystal of great interest at an X-ray free-electron laser," said Sebastien Boutet, a scientist at the SLAC National Accelerator Laboratory.
The new images highlighted four protein hot spots key in the activation of BinAB's toxicity.
The intestines of Aedes mosquitos, the species that carries Zika, is without the receptors that allows BinAB to bind and dissolve inside the intestine. The new information may allow researchers to manipulate the structure of BinAB so that's its toxic hotspots are activated by a different set of receptors.
"With the results of the study, we now feel more confident that we can design the protein to target Aedes mosquitoes," Colletier concluded.