Chapter 9 : Receptors for Bacterial Toxins

The figure depicts the binding and entry of BL22 into a leukemia cell expressing CD22. Once taken into an endosome, BL22 is processed by the cellular protease, furin. This is followed by the reduction of a key disulfide (Cys-265 to 287), the release of an enzymatically active C-terminal fragment, its translocation to the cytosol, and the cessation of protein synthesis. This causes death of the leukemia cell.

Structure of lowdensity LRP, the receptor for Pseudomonas exotoxin A. LRP is a multifunctional scavenger receptor capable of binding a variety of ligands to different clusters of ligand-binding repeats. tPA, tissue plasminogen activator; LPL, lipoprotein lipase. From reference 2 with permission.

RAP blocks binding and toxicity of PEA for mouse LM fibroblasts. (A) Inhibition by RAP-GST of PEA binding to mouse LM cells. LM cell monolayers were incubated with medium containing RAP-GST (●) or GST (○) for 18 h at 4°C, followed by incubation with 2 µg/ml of PEA for 5 h at 4°C. Cells were then washed, harvested, and homogenized, and the concentration of cellassociated toxin assayed by enzyme-linked immunosorbent assay. (B) RAP protects LM cells from PEA-induced toxicity. Various concentrations of RAP were preincubated with LM cells for 90 min at 37°C. Cells were cooled and 40 ng of PEA added. Protein synthesis was assessed by measuring incorporation of 3H-leucine into trichloroacetic acid-precipitable material. From reference 3 with permission.

Structure of the cell surfaceexpressed precursor form of the heparinbinding EGF-like growth factor, the DT receptor.

Proposed model for role of CD9 and heparin-like molecules in binding of DT to proHB-EGF. (a) ProHB-EGF alone in the plasma membrane cannot bind DT. (b) CD9 binds to and orients proHB-EGF so that it is accessible to DT. (c) Cell surface heparan-sulfate proteoglycans (HSPG) or free heparin binds to proHB-EGF at the heparin-binding domain and induces a conformational change; this change results in increased affinity of the receptor for DT. (d) The proHB-EGF/CD9-HSPG-DT complex is formed. From reference 8 with permission.

Structure of Gb3. Gb3 consists of a ceramide long-chain fatty acid that is embedded in the plasma membrane and a short extracellular trisaccharide chain ending in a digalactose residue. From reference 4 with permission.