Crystal structures combined with biochemical data show that the δ-endotoxins from Bacillus thuringiensis are structurally poised towards large-scale, irreversible conformational changes that transform them from the soluble protein bound at the cell surface into a membrane-embedded form causing lysis of susceptible insect cells. Cry δ-endotoxins are made of a helix bundle, a β-prism and a β-sandwich. The conformational change involves an umbrella-like opening between the helix-4,5-hairpin and the remaining helices, and between the helical domain and the two sheet domains. Comparison of Cry1Ac structures with and without the bound receptor ligand GalNAc associates occupation of the high-affinity site on the β-sandwich with an increase of temperature factors in the helical, pore-forming domain, which may indicate how receptor binding could trigger the required major conformational change. The structure of Cyt δ-endotoxins indicates that the surface helix hairpins must peel away to expose the β-strands for membrane attack. Single amino acid substitutions in hinge residues or the core can restore activity following an inhibitory mutation.

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