Cadherin receptor binding

CrylAa CrylA loop2 Receptor binding, toxicity, specificity Cadherin receptor binding, toxin activation, oligomeric and pre-pore formation, toxin insertion [74,183,184] [61,81]... 

Figure 7.30 Mode of action of Cry toxins. (a,b) Crystals are solubilized and activated to give rise to the monomeric toxin, (c) The toxin monomer binds in cadherin receptor, followed by proteolytic cleavage of helix a-1. (d) The tetramer is formed by inter monomeric contacts, (e) The toxin oligomer binds to the aminopeptidase-N receptor (APN receptor). The APN receptor and oligomeric Cry toxin localize to lipid rafts, (f) Following a conformational change, the oligomer inserts into membrane, forming a tetrameric pore. (From Bravo et al., in Comprehensive Molecular Insect Science, Gilbert, L.I., Iatrou, K., and Gill, S.S., Eds., Vol. 6, Elsevier, London, 2005, p. 175. With permission.)...

Membrane receptor binding Cadherin receptor mutation [149]... 

The active toxin has two main functional entities, responsible for receptor binding and ion channel activity, respectively. The activated toxin binds to receptors, which seem to be of different types, on the midgut microvilli of the susceptible insects. Different toxins seem to bind to different receptor proteins that may be an enzyme such as aminopeptidase or alkaline phosphatase, or a cadherin-like membrane protein. (The cadherins are proteins that are important in keeping the cells together by mediating Ca+-dependent cell-cell adhesion in animal tissue.) The toxins are anchored to the outer epithelial cell membrane in such a way that the membrane is perforated by pores or channels where ions can freely pass. This model proposes that an influx of water, along with ions, results in swelling and lysis. The epithelium is destroyed and the insect rots. 

FIGURE 34.2 Illustration of cadherin receptors associated with actin cytoskeleton. Cadherin dimers are shown in a linear zipper structure with antiparallel binding of the ECl domains. Cytopiasmic taiis of cadherins interact with actin filaments through structural proteins -catenin, pl20 catenin, plakoglobin, and a-catenin. 

Several nonconventional cadherins that contain cadherin repeats have been described but they have specific features not found in the classical cadherins [1]. The cadherin Flamingo, originally detected in Drosophila, contains seven transmembrane segments and in this respect resembles G protein-coupled receptors. The extracellular domain of Flamingo and its mammalian homologs is composed of cadherin repeats as well as EGF-like and laminin motifs. The seven transmembrane span cadherins have a role in homotypic cell interactions and in the establishment of cell polarity. The FAT-related cadherins are characterized by a large number of cadherin repeats (34 in FAT and 27 in dachsous). Their cytoplasmic domains can bind to catenins. T- (=truncated-)cadherin differs from other cadherins in that it has no transmembrane domain but is attached to the cell membrane via a glycosylpho-sphatidylinositol anchor. 

Adhesion molecules such as LI, neural cell adhesion molecule (N-CAM) and N-cadherin promote axonal regeneration by homophilic interactions between axons and Schwann cell surfaces (see Ch. 7). The expression of p75 (low affinity NGF receptor, Ch. 27) is also increased at the Schwann cell surface after injury. Extracellular matrix molecules, such as tenascin and proteoglycans, increase the regenerative potential of damaged peripheral nerves by binding to integrins on the axonal surface. 

E-cadherin is unique in that it not only, like other cadherin family members, mediates homophilic adhesion to establish and maintain cellcell contacts, it also serves as a counter-receptor for integrins Oe/37 (Cepek et al, 1994) and (Whittard et al, 2002) in heterophilic adhesion. In fact, the interaction between E-cadherin on mucosal epithelial cells and Oe/S on intraepithelial lymphocytes has been the best characterized tissue-specific interaction for lymphocyte retention. Although structure of binding domains between E-cadherin and is not available, mutagenesis... 

Anders, J., Kjar, S., and Ibanez, G. F. (2001). Molecular modeling of the extracellular domain of the RET receptor tyrosine kinase reveals multiple cadherin-like domains and a calcium-binding site./. Biol. Chem. 276, 35808-35817. 

Two single substitutions in the listerial invasion protein InlA increase its binding affinity by four orders of magnitude and extend its binding specificity to formerly incompatible murine receptor E-cadherin [30],... 

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