title: Univalent binding of the Cry1Ab toxin of Bacillus thuringiensis to a conserved structural motif in the cadherin receptor BT-R1.
abstract: The Cry1Ab toxin produced by Bacillus thuringiensis (Bt) exerts insecticidal action upon binding to BT-R1, a cadherin receptor localized in the midgut epithelium of the tobacco hornworm Manduca sexta [Dorsch, J. A., Candas, M., Griko, N. B., Maaty, W. S., Midboe, E. G., Vadlamudi, R. K., and Bulla, L. A., Jr. (2002) Cry1A toxins of Bacillus thuringiensis bind specifically to a region adjacent to the membrane-proximal extracellular domain of BT-R1 in Manduca sexta: involvement of a cadherin in the entomopathogenicity of Bacillus thuringiensis, Insect Biochem. Mol. Biol. 32, 1025-1036]. BT-R1 represents a family of invertebrate cadherins whose ectodomains (ECs) are composed of multiple cadherin repeats (EC1 through EC12). In the present work, we determined the Cry1Ab toxin binding site in BT-R1 in the context of cadherin structural determinants. Our studies revealed a conserved structural motif for toxin binding that includes two distinct regions within the N- and C-termini of EC12. These regions are characterized by unique sequence signatures that mark the toxin-binding function in BT-R1 as well as in homologous lepidopteran cadherins. Structure modeling of EC12 discloses the conserved motif as a single broad interface that holds the N- and C-termini in close proximity. Binding of toxin to BT-R1, which is univalent, and the subsequent downstream molecular events responsible for cell death depend on the conserved motif in EC12.
authors: Biological Targets, Inc., Pilot Point, Texas 76258, USA.
authors: Natalya B
authors: NB
authors: Griko
authors: Laura
authors: L
authors: Rose-Young
authors: Xuebin
authors: X
authors: Zhang
authors: Lindy
authors: L
authors: Carpenter
authors: Mehmet
authors: M
authors: Candas
authors: Mohamed A
authors: MA
authors: Ibrahim
authors: Matthew
authors: M
authors: Junker
authors: Lee A
authors: LA
authors: Bulla
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D001413:Bacillus thuringiensis / Q000378:metabolism*; D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D015820:Cadherins / Q000737:chemistry* / Q000378:metabolism; D003001:Cloning, Molecular; D017124:Conserved Sequence; D004731:Endotoxins / Q000737:chemistry* / Q000378:metabolism; D006460:Hemolysin Proteins / Q000737:chemistry* / Q000378:metabolism; D007814:Larva; D018402:Manduca / Q000196:embryology / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D010572:Pest Control, Biological; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D020449:Repetitive Sequences, Amino Acid; D012680:Sensitivity and Specificity
chemical_list: D000083722:Bacillus thuringiensis Toxins; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D015820:Cadherins; D004731:Endotoxins; D006460:Hemolysin Proteins; D010455:Peptides; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C030956:insecticidal crystal protein, Bacillus Thuringiensis