6T19

Structure of mosquitocidal Cyt1A protoxin obtained by Serial Femtosecond Crystallography on in vivo grown crystals soaked with DTT at pH 7

This is a non-PDB format compatible entry.

Summary for 6T19

• Entry DOI: 10.2210/pdb6t19/pdb
• Descriptor: Type-1Aa cytolytic delta-endotoxin, SODIUM ION (3 entities in total)
• Functional Keywords: mosquitocidal toxin, in vivo grown nanocrystals, toxin
• Biological source: Bacillus thuringiensis subsp. israelensis
• Total number of polymer chains: 1
• Total formula weight: 27377.95

Authors

Tetreau, G.,Banneville, A.S.,Andreeva, E.,Brewster, A.S.,Hunter, M.S.,Sierra, R.G.,Young, I.D.,Boutet, S.,Coquelle, N.,Cascio, D.,Sawaya, M.R.,Sauter, N.K.,Colletier, J.P. (deposition date: 2019-10-03, release date: 2020-10-14, Last modification date: 2024-01-24)

Primary citation

Tetreau, G.,Banneville, A.S.,Andreeva, E.A.,Brewster, A.S.,Hunter, M.S.,Sierra, R.G.,Teulon, J.M.,Young, I.D.,Burke, N.,Grunewald, T.A.,Beaudouin, J.,Snigireva, I.,Fernandez-Luna, M.T.,Burt, A.,Park, H.W.,Signor, L.,Bafna, J.A.,Sadir, R.,Fenel, D.,Boeri-Erba, E.,Bacia, M.,Zala, N.,Laporte, F.,Despres, L.,Weik, M.,Boutet, S.,Rosenthal, M.,Coquelle, N.,Burghammer, M.,Cascio, D.,Sawaya, M.R.,Winterhalter, M.,Gratton, E.,Gutsche, I.,Federici, B.,Pellequer, J.L.,Sauter, N.K.,Colletier, J.P.
Serial femtosecond crystallography on in vivo-grown crystals drives elucidation of mosquitocidal Cyt1Aa bioactivation cascade.
Nat Commun, 11:1153-1153, 2020

PubMed 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.

PubMed: 32123169
DOI: 10.1038/s41467-020-14894-w

Experimental method

X-RAY DIFFRACTION (1.85 Å)