Serial femtosecond crystallography on in vivo-grown crystals drives elucidation of mosquitocidal Cyt1Aa bioactivation cascade - Archive ouverte HAL Access content directly
Journal Articles Nature Communications Year : 2020

Serial femtosecond crystallography on in vivo-grown crystals drives elucidation of mosquitocidal Cyt1Aa bioactivation cascade

Luca Signor
Daphna Fenel
Manfred Burghammer
  • Function : Author
  • PersonId : 963561
Mathias Winterhalter
Irina Gutsche
Jean-Luc Pellequer

Abstract

Cyt1Aa is the one of four crystalline protoxins produced by mosquitocidal bacterium Bacillus thuringiensis israelensis (Bti) that has been shown to delay the evolution of insect resistance in the field. Limiting our understanding of Bti efficacy and the path to improved toxicity and spectrum has been ignorance of how Cyt1Aa crystallizes in vivo and of its mechanism of toxicity. Here, we use serial femtosecond crystallography to determine the Cyt1Aa protoxin structure from sub-micron-sized crystals produced in Bti. Structures determined under various pH/redox conditions illuminate the role played by previously uncharacterized disulfide-bridge and domain-swapped interfaces from crystal formation in Bti to dissolution in the larval mosquito midgut. Biochemical, toxicological and biophysical methods enable the deconvolution of key steps in the Cyt1Aa bioactivation cascade. We additionally show that the size, shape, production yield, pH sensitivity and toxicity of Cyt1Aa crystals grown in Bti can be controlled by single atom substitution.
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hal-02506591 , version 1 (19-11-2020)

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Guillaume Tetreau, Anne-Sophie Banneville, Elena Andreeva, Aaron Brewster, Mark Hunter, et al.. Serial femtosecond crystallography on in vivo-grown crystals drives elucidation of mosquitocidal Cyt1Aa bioactivation cascade. Nature Communications, 2020, 11 (1), ⟨10.1038/s41467-020-14894-w⟩. ⟨hal-02506591⟩
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