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PMID:24453976
| Citation |
Piteau, M, Papatheodorou, P, Schwan, C, Schlosser, A, Aktories, K and Schmidt, G (2014) Lu/BCAM Adhesion Glycoprotein Is a Receptor for Escherichia coli Cytotoxic Necrotizing Factor 1 (CNF1). PLoS Pathog. 10:e1003884 |
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| Abstract |
The Cytotoxic Necrotizing Factor 1 (CNF1) is a protein toxin which is a major virulence factor of pathogenic Escherichia coli strains. Here, we identified the Lutheran (Lu) adhesion glycoprotein/basal cell adhesion molecule (BCAM) as cellular receptor for CNF1 by co-precipitation of cell surface molecules with tagged toxin. The CNF1-Lu/BCAM interaction was verified by direct protein-protein interaction analysis and competition studies. These studies revealed amino acids 720 to 1014 of CNF1 as the binding site for Lu/BCAM. We suggest two cell interaction sites in CNF1: first the N-terminus, which binds to p37LRP as postulated before. Binding of CNF1 to p37LRP seems to be crucial for the toxin's action. However, it is not sufficient for the binding of CNF1 to the cell surface. A region directly adjacent to the catalytic domain is a high affinity interaction site for Lu/BCAM. We found Lu/BCAM to be essential for the binding of CNF1 to cells. Cells deficient in Lu/BCAM but expressing p37LRP could not bind labeled CNF1. Therefore, we conclude that LRP and Lu/BCAM are both required for toxin action but with different functions. |
| Links |
PubMed PMC3894216 Online version:10.1371/journal.ppat.1003884 |
| Keywords |
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| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:0008022: protein C-terminus binding |
ECO:0000314: |
F |
Cells not expressing Lu/BCAM did not respond to CNF1 toxin. The data indicated that the toxin (CNF1) specifically binds to Lu/BCAM (figure 4). MALDI-TOF analysis of the precipitate identified Lu/BCAM as an interaction partner for CNF1. It was suggested that there are two interaction sites in CNF1: The N-terminus binding to 37LRP/67LR and the C-terminus binding with high affinity to Lu/BCAM. The interaction of CNF1 Lu/BCAM was verified using several methods: Western blotting, immunofluorescence, MALDI-TOF analysis, and fluorescence activated cell sorting (FACS) analysis. |
complete | ||||
| GO:0019534: toxin transporter activity |
ECO:0000314: |
F |
Figure 3. Lu/BCAM is crucial for binding and uptake of CNF1. |
complete | ||||
|
enables |
GO:0008022: protein C-terminus binding |
ECO:0000314: direct assay evidence used in manual assertion |
F |
Seeded From UniProt |
complete | |||
See also
References
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