Institut de Biologie StructuraleGrenoble / France

Structural and functional insights into Cyt1Aa, a naturally crystallin insecticidal protein

How can mosquito populations be reduced without impacting the environment or inducing resistance ? This double challenge is met by mosquitocidal bacterium Bacillus thuringiensis israelensis (Bti), which produces, in the form of nanocrystals, four toxins that specifically target mosquito larvae, thereby preventing the transmission of serious diseases such as malaria, dengue fever or chikungunya. Among the four toxins produced by Bti, researchers from a consortium of 11 laboratories led by the Institute of Structural Biology focused on the Cyt1Aa toxin, thanks to which Bti escapes the resistance of mosquitoes. By combining several structural biology approaches (femtosecond serial crystallography at an X-ray free electron laser (XFEL) and complementary biochemical, biophysical and toxicological methods in combination with mutagenisis), they elucidate the full Cyt1Aa bioactivation cascade, from in vivo crystallization to its toxic activity in the target insect. This study, published on March 2, 2020, in the journal Nature Communications, pave the way for a rational tailoring of its properties to human needs.

Serial femtosecond crystallography on in vivo-grown crystals drives elucidation of mosquitocidal Cyt1Aa bioactivation cascade. Tetreau G, Banneville AS, Andreeva EA, Brewster AS, Hunter MS, Sierra RG, Teulon JM, Young ID, Burke N, Gruenewald TA, Beaudouin J, Snigireva I, Fernandez-Luna MT, Burt A, Park HW, Signor L, Bafna JA, Sadir R, Fenel D, Boeri-Erba E, Rosenthal M, Coquelle N, Burghammer M, Cascio D, Sawaya MR, Winterhalter M, Gratton E, Gutsch I, Federici B, Pellequer JL, Sauter NK, Colletier JP. Nature Communications ; 11, 1153